Molecular in situ topology of Aczonin/Piccolo and associated proteins at the mammalian neurotransmitter release site

The protein machinery of neurotransmitter exocytosis requires efficient orchestration in space and time, for speed and precision of neurotransmission and also for synaptic ontogeny and plasticity. However, its spatial organization in situ is virtually unknown. Aczonin/Piccolo is a putative organizer...

Full description

Saved in:
Bibliographic Details
Published inProceedings of the National Academy of Sciences - PNAS Vol. 108; no. 31; pp. E392 - E401
Main Authors Limbach, Christoph, Laue, Michael M, Wang, Xiaolu, Hu, Bin, Thiede, Nadine, Hultqvist, Greta, Kilimann, Manfred W
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 02.08.2011
National Acad Sciences
SeriesPNAS Plus
Subjects
Adaptor Proteins, Signal Transducing - metabolism
Animals
Binding Sites
Biological Sciences
Cell Membrane - metabolism
Cell Membrane - ultrastructure
Cytoskeletal Proteins - metabolism
electron microscopy
exocytosis
GTP-Binding Proteins - metabolism
Immunoblotting
Mammals
MEDICIN
MEDICINE
Membranes
Microscopy, Immunoelectron
Molecular structure
Multiprotein Complexes - metabolism
Multiprotein Complexes - ultrastructure
Nerve Tissue Proteins - metabolism
Neuropeptides - metabolism
Neurotransmitter Agents - metabolism
Neurotransmitters
ontogeny
plasma membrane
PNAS Plus
polypeptides
Protein Binding
protein structure
Proteins
Rats
Rats, Sprague-Dawley
scaffolding protein
space and time
Synapses - metabolism
Synapses - ultrastructure
synaptic transmission
topology
Online AccessGet full text

Cover

Abstract The protein machinery of neurotransmitter exocytosis requires efficient orchestration in space and time, for speed and precision of neurotransmission and also for synaptic ontogeny and plasticity. However, its spatial organization in situ is virtually unknown. Aczonin/Piccolo is a putative organizer protein of mammalian active zones. We determined by immunogold electron microscopy (EM) (i) the spatial arrangement (i.e., topology) of 11 segments of the Aczonin polypeptide in situ, and correlated it to (ii) the positioning of Aczonin-interacting domains of Bassoon, CAST/ELKS, Munc13, and RIM and (iii) the ultrastructurally defined presynaptic macromolecular aggregates known as dense projections and synaptic ribbons. At conventional synapses, Aczonin assumes a compact molecular topology within a layer 35 to 80 nm parallel to the plasma membrane (PM), with a "trunk" sitting on the dense projection top and a C-terminal "arm" extending down toward the PM and sideward to the dense projection periphery. At ribbon synapses, Aczonin occupies the whole ribbon area. Bassoon colocalizes with Aczonin at conventional synapses but not at ribbon synapses. At both conventional and ribbon synapses, CAST, Munc13, and RIM are segregated from Aczonin, closer to the PM, and Aczonin is positioned such that it may control the access of neurotransmitter vesicles to the fusion site.
AbstractList The protein machinery of neurotransmitter exocytosis requires efficient orchestration in space and time, for speed and precision of neurotransmission and also for synaptic ontogeny and plasticity. However, its spatial organization in situ is virtually unknown. Aczonin/Piccolo is a putative organizer protein of mammalian active zones. We determined by immunogold electron microscopy (EM) ( i ) the spatial arrangement (i.e., topology) of 11 segments of the Aczonin polypeptide in situ, and correlated it to ( ii ) the positioning of Aczonin-interacting domains of Bassoon, CAST/ELKS, Munc13, and RIM and ( iii ) the ultrastructurally defined presynaptic macromolecular aggregates known as dense projections and synaptic ribbons. At conventional synapses, Aczonin assumes a compact molecular topology within a layer 35 to 80 nm parallel to the plasma membrane (PM), with a “trunk” sitting on the dense projection top and a C-terminal “arm” extending down toward the PM and sideward to the dense projection periphery. At ribbon synapses, Aczonin occupies the whole ribbon area. Bassoon colocalizes with Aczonin at conventional synapses but not at ribbon synapses. At both conventional and ribbon synapses, CAST, Munc13, and RIM are segregated from Aczonin, closer to the PM, and Aczonin is positioned such that it may control the access of neurotransmitter vesicles to the fusion site.
The protein machinery of neurotransmitter exocytosis requires efficient orchestration in space and time, for speed and precision of neurotransmission and also for synaptic ontogeny and plasticity. However, its spatial organization in situ is virtually unknown. Aczonin/Piccolo is a putative organizer protein of mammalian active zones. We determined by immunogold electron microscopy (EM) (i) the spatial arrangement (i. e., topology) of 11 segments of the Aczonin polypeptide in situ, and correlated it to (ii) the positioning of Aczonin-interacting domains of Bassoon, CAST/ELKS, Munc13, and RIM and (iii) the ultrastructurally defined presynaptic macromolecular aggregates known as dense projections and synaptic ribbons. At conventional synapses, Aczonin assumes a compact molecular topology within a layer 35 to 80 nm parallel to the plasma membrane (PM), with a "trunk" sitting on the dense projection top and a C-terminal "arm" extending down toward the PM and sideward to the dense projection periphery. At ribbon synapses, Aczonin occupies the whole ribbon area. Bassoon colocalizes with Aczonin at conventional synapses but not at ribbon synapses. At both conventional and ribbon synapses, CAST, Munc13, and RIM are segregated from Aczonin, closer to the PM, and Aczonin is positioned such that it may control the access of neurotransmitter vesicles to the fusion site.
The protein machinery of neurotransmitter exocytosis requires efficient orchestration in space and time, for speed and precision of neurotransmission and also for synaptic ontogeny and plasticity. However, its spatial organization in situ is virtually unknown. Aczonin/Piccolo is a putative organizer protein of mammalian active zones. We determined by immunogold electron microscopy (EM) (i) the spatial arrangement (i.e., topology) of 11 segments of the Aczonin polypeptide in situ, and correlated it to (ii) the positioning of Aczonin-interacting domains of Bassoon, CAST/ELKS, Munc13, and RIM and (iii) the ultrastructurally defined presynaptic macromolecular aggregates known as dense projections and synaptic ribbons. At conventional synapses, Aczonin assumes a compact molecular topology within a layer 35 to 80 nm parallel to the plasma membrane (PM), with a "trunk" sitting on the dense projection top and a C-terminal "arm" extending down toward the PM and sideward to the dense projection periphery. At ribbon synapses, Aczonin occupies the whole ribbon area. Bassoon colocalizes with Aczonin at conventional synapses but not at ribbon synapses. At both conventional and ribbon synapses, CAST, Munc13, and RIM are segregated from Aczonin, closer to the PM, and Aczonin is positioned such that it may control the access of neurotransmitter vesicles to the fusion site. [PUBLICATION ABSTRACT]
The protein machinery of neurotransmitter exocytosis requires efficient orchestration in space and time, for speed and precision of neurotransmission and also for synaptic ontogeny and plasticity. However, its spatial organization in situ is virtually unknown. Aczonin/Piccolo is a putative organizer protein of mammalian active zones. We determined by immunogold electron microscopy (EM) ( i ) the spatial arrangement (i.e., topology) of 11 segments of the Aczonin polypeptide in situ, and correlated it to ( ii ) the positioning of Aczonin-interacting domains of Bassoon, CAST/ELKS, Munc13, and RIM and ( iii ) the ultrastructurally defined presynaptic macromolecular aggregates known as dense projections and synaptic ribbons. At conventional synapses, Aczonin assumes a compact molecular topology within a layer 35 to 80 nm parallel to the plasma membrane (PM), with a “trunk” sitting on the dense projection top and a C-terminal “arm” extending down toward the PM and sideward to the dense projection periphery. At ribbon synapses, Aczonin occupies the whole ribbon area. Bassoon colocalizes with Aczonin at conventional synapses but not at ribbon synapses. At both conventional and ribbon synapses, CAST, Munc13, and RIM are segregated from Aczonin, closer to the PM, and Aczonin is positioned such that it may control the access of neurotransmitter vesicles to the fusion site. Author Summary The model in Fig. P1 E shows that the molecular dimensions of Aczonin correspond strikingly to the sizes of dense projections (45 nm high) and synaptic vesicles (38 nm diameter). The “trunk-and-arm” topology in particular suggests that Aczonin acts as a gatekeeper for vesicles to access the plasma membrane from deep within the terminal before release. This notion is consistent with recent functional studies from other laboratories ( 4 , 5 ). Our work reveals, for a subset of presynaptic proteins, a well defined molecular organization at the neurotransmitter release site. Future research will aim to complete this model by determining the topologies of additional proteins and protein segments, and to study the molecular topologies of other specialized synapse types such as the neuromuscular junction. A particular challenge will be to observe this molecular machinery in motion during vesicle exocytosis. With its huge size, Aczonin was particularly promising as a potential organizer of the presynaptic molecular machinery. The protein's long polypeptide chain, were it an extended α-helical filament, could theoretically extend 20 vesicle diameters into the synaptic terminal. However, what is the spatial arrangement (i.e., the molecular topology) of this large molecule at the active zone? To investigate this topology, we raised antibodies against 11 recombinant partial sequences along the Aczonin polypeptide and used them as specific molecular probes, to label the corresponding segments of Aczonin in brain sections that we subsequently examined with EM. As seen in Fig. P1 A , Aczonin segments were detected at sharply defined distances from the presynaptic plasma membrane. We quantified localizations with morphometric measurements of the positions of several hundred immunolabel particles for each protein segment. The entire Aczonin molecule was found to occupy a layer of 35 to 80 nm parallel to the plasma membrane, with the N-terminal parts of the protein further away ( Fig. P1 B ) and the C-terminal part closer to the membrane ( Fig. P1 C ). Immunolabeling of Aczonin sequences combined with staining dense projections with heavy metals ( Fig. P1 B – D ) allowed us to also determine the lateral localizations relative to the central axis of dense projections. We found that the N-terminal sequences of Aczonin sit right above dense projections ( Fig. P1 B ) and constitute a “trunk,” whereas the C-terminal sequences reach in an “arm”-like manner toward the interval between dense projections ( Fig. P1 C ) where neurotransmitter vesicles are believed to fuse. These findings led us to the model illustrated in Fig. P1 E . Sequence region 7–6 of Aczonin is known to interact with the N-terminal regions of Munc13 and RIM, and the C-terminal part of Bassoon. Therefore, we also determined the localizations of these protein segments. The Bassoon C terminus colocalized very closely with the corresponding Aczonin region, whereas the RIM and Munc13 N termini ( Fig. P1 D ), as well as a segment of the voltage-gated calcium channel (another important player in neurotransmitter release), were significantly closer to the plasma membrane. We complemented these studies by determining the topology of Aczonin and its binding partners at a specialized synapse type: ribbon synapses of photoreceptor cells in the eye. Aczonin/Piccolo, Bassoon, CAST, Munc13, and RIM are among the presynaptic proteins that participate in neurotransmitter release. These molecules are large and complex (Aczonin and Bassoon are among the largest proteins known, with lengths of 5000 and 4000 aa, respectively), and can bind to many other proteins including each other, giving rise to a highly interconnected and interactive supramolecular assembly ( 3 ). In our study, we set out to explore the spatial organization of this assembly at the neurotransmitter release site using immunogold EM. Many proteins that contribute to neurotransmitter release have been identified in recent years ( 1 ), but our understanding of the mechanistic interplay between these proteins is still in its infancy. Moreover, it appears that these molecules are assembled in an organized fashion that enhances the speed and precision of protein interactions and turns them into small “molecular machines.” For example, electron microscopists discovered half a century ago that specific staining techniques can visualize presynaptic aggregates of regular size, shape, and spacing ( Fig. P1 B – D ) ( 2 ). Many researchers suspect that these aggregates, called dense projections, represent modular, structured assemblies of the neurotransmitter release machinery. Neurotransmitter release is very fast—an electrical signal can trigger membrane fusion in less than 1 ms—but at the same time highly controlled and regulated. This requires the precise interplay of hundreds of different proteins at defined patches of the presynaptic plasma membrane known as active zones. Modulating the quantities and properties of active zone proteins fine-tunes synaptic signaling for information processing and memory tasks. Disturbances in the function of active zone proteins have been implicated in medical disorders such as ALS, schizophrenia, depression, and diabetes. Synapses serve as junctions through which nerve cells send signals to other nerve cells, to muscle cells, or to hormone-secreting cells. At the end of a nerve fiber, a synaptic terminal ( Fig. P1 A ) contains a cluster of several hundred small membrane vesicles filled with neurotransmitter substances. Electrical signals arrive at the terminals and induce some of these vesicles to fuse with the presynaptic plasma membrane, which discharges the neurotransmitter into the synaptic cleft. Transmitter molecules can then bind to receptor proteins on the opposing postsynaptic membrane and induce a new electrical signal in the postsynaptic cell.
Author Hultqvist, Greta
Limbach, Christoph
Laue, Michael M
Kilimann, Manfred W
Hu, Bin
Wang, Xiaolu
Thiede, Nadine
Author_xml – sequence: 1
  fullname: Limbach, Christoph
– sequence: 2
  fullname: Laue, Michael M
– sequence: 3
  fullname: Wang, Xiaolu
– sequence: 4
  fullname: Hu, Bin
– sequence: 5
  fullname: Thiede, Nadine
– sequence: 6
  fullname: Hultqvist, Greta
– sequence: 7
  fullname: Kilimann, Manfred W
BackLink https://www.ncbi.nlm.nih.gov/pubmed/21712437$$D View this record in MEDLINE/PubMed
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-157245$$DView record from Swedish Publication Index
BookMark eNp9kktvEzEUhS1URNPAmh1YbGBBmutHZuwNUlTKQyoCicLWcjye1NWMPbU9oPLr8SihoSxYWfL97rmvc4KOfPAWoacETgnUbDl4nU4JAVJDTUA8QDMCkiwqLuEIzQBovRCc8mN0ktI1AMiVgEfomJKaUM7qGcqfQmfN2OmIncfJ5RHnMIQubG9xaPHa_Are-eUXZ0z5xNo3WKcUjNPZNniIIVvnE9YZ5yuLe933unPaY2_HEovap97lbCOOtrM62amEfYwetrpL9sn-naPLd-eXZx8WF5_ffzxbXyxMBSwvOF8xqFrBQUKz4VKAqFdWslZoag1vNedCgm7aRmwEGCk2ILjYcFPblpOKzdHrnWz6aYdxo4boeh1vVdBOvXXf1yrErRpHRVY1LaXm6M0OL2xvG2N96b-7l3U_4t2V2oYfipFVWTopAi_3AjHcjDZl1btkbNdpb8OYlBDlRDWHqbNX_yXLERmvCGNQ0Bf_oNdhjL6sbdKjUjA6VV7uIBNDStG2d10TUJNR1GQUdTBKyXj297B3_B9nFOD5HpgyD3KijKvOmaQHotVB6W10SX37SoFUAERSKEV-A-fk0K8
CitedBy_id crossref_primary_10_1523_JNEUROSCI_0658_15_2015
crossref_primary_10_1002_bies_201100135
crossref_primary_10_3390_ijms20092147
crossref_primary_10_1002_jnr_24650
crossref_primary_10_3389_fnsyn_2017_00014
crossref_primary_10_3389_fnmol_2022_838311
crossref_primary_10_3389_fnmol_2021_744034
crossref_primary_10_1007_s00441_014_2102_7
crossref_primary_10_1073_pnas_1812029116
crossref_primary_10_1523_JNEUROSCI_5128_12_2013
crossref_primary_10_1152_physrev_00026_2018
crossref_primary_10_1038_s41598_018_29879_5
crossref_primary_10_1016_j_conb_2011_10_005
crossref_primary_10_1523_JNEUROSCI_1291_23_2024
crossref_primary_10_1016_j_jmb_2022_167629
crossref_primary_10_1007_s00018_014_1657_5
crossref_primary_10_1016_j_neures_2017_11_014
crossref_primary_10_1016_j_neuroscience_2015_05_047
crossref_primary_10_3389_fncel_2015_00196
crossref_primary_10_3389_fnsyn_2020_00032
crossref_primary_10_3390_ijms25137443
crossref_primary_10_1371_journal_pone_0070373
crossref_primary_10_15252_embr_202256702
crossref_primary_10_1016_j_neuron_2012_06_012
crossref_primary_10_1016_j_tins_2012_10_001
crossref_primary_10_1016_j_cell_2024_03_003
crossref_primary_10_1152_physrev_00039_2020
crossref_primary_10_7554_eLife_29275
crossref_primary_10_1038_s41593_017_0041_9
crossref_primary_10_1152_physrev_00032_2016
crossref_primary_10_1002_embj_201385887
crossref_primary_10_1146_annurev_vision_082114_035709
crossref_primary_10_1038_srep27935
crossref_primary_10_1126_sciadv_abl7560
crossref_primary_10_3389_fnsyn_2015_00019
crossref_primary_10_1016_j_neuropharm_2021_108622
crossref_primary_10_1038_onc_2017_15
crossref_primary_10_3389_fncel_2015_00007
crossref_primary_10_1016_j_neuron_2016_07_042
crossref_primary_10_1021_acs_chemrev_6b00629
crossref_primary_10_1016_j_molcel_2020_10_029
crossref_primary_10_1038_s41598_024_60257_6
crossref_primary_10_3389_fncel_2014_00259
crossref_primary_10_1523_JNEUROSCI_3267_12_2012
crossref_primary_10_1016_j_yexcr_2015_02_011
crossref_primary_10_1002_1873_3468_13258
crossref_primary_10_18632_aging_202861
crossref_primary_10_3390_genes13030499
Cites_doi 10.1007/BF00266584
10.1016/j.proghi.2006.09.001
10.1002/cne.20893
10.1523/JNEUROSCI.1255-09.2009
10.1002/cne.1344
10.1046/j.1460-9568.1999.00793.x
10.1111/j.1365-2818.1986.tb02766.x
10.1083/jcb.200711167
10.1016/S0022-5320(68)90027-0
10.1083/jcb.200408157
10.1002/cne.21915
10.1016/j.tins.2006.08.006
10.1016/j.jmb.2007.10.029
10.1016/j.neuroscience.2006.04.061
10.1016/S0006-8993(01)02078-9
10.1523/JNEUROSCI.3235-08.2008
10.1177/39.6.1709656
10.1083/jcb.200908082
10.1007/s00441-006-0244-y
10.1523/JNEUROSCI.4639-07.2008
10.1111/j.1471-4159.2009.05888.x
10.1083/jcb.147.1.151
10.1006/bbrc.2000.3256
10.1111/j.1460-9568.2004.03198.x
10.1083/jcb.108.1.111
10.1177/29.7.6167611
10.1146/annurev.cellbio.23.090506.123417
10.1016/S0896-6273(00)80883-1
10.1016/j.neuron.2009.09.019
10.1523/JNEUROSCI.1773-07.2007
10.1073/pnas.1002307107
10.1016/j.neuron.2007.06.013
10.1152/physiol.00014.2004
10.1093/oso/9780199632190.003.0009
10.1016/j.neuron.2010.10.026
10.1016/0896-6273(88)90140-7
10.1016/j.neuron.2010.11.021
10.1074/jbc.M100929200
10.1016/S0896-6273(00)80520-6
10.1016/0306-4522(91)90143-C
10.1016/S0896-6273(01)00450-0
10.1038/35054000
10.1523/JNEUROSCI.2495-10.2010
10.1016/0306-4522(82)90035-5
10.1016/S0896-6273(03)00062-X
10.1007/978-1-4684-0123-3_4
10.1016/S0896-6273(03)00086-2
10.1002/cne.21975
10.1177/40.12.1453003
10.1083/jcb.200812150
ContentType Journal Article
Copyright Copyright National Academy of Sciences Aug 2, 2011
Copyright_xml – notice: Copyright National Academy of Sciences Aug 2, 2011
DBID FBQ
CGR
CUY
CVF
ECM
EIF
NPM
AAYXX
CITATION
7QG
7QL
7QP
7QR
7SN
7SS
7T5
7TK
7TM
7TO
7U9
8FD
C1K
FR3
H94
M7N
P64
RC3
7X8
5PM
ADTPV
AOWAS
DF2
DOI 10.1073/pnas.1101707108
DatabaseName AGRIS
Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
CrossRef
Animal Behavior Abstracts
Bacteriology Abstracts (Microbiology B)
Calcium & Calcified Tissue Abstracts
Chemoreception Abstracts
Ecology Abstracts
Entomology Abstracts (Full archive)
Immunology Abstracts
Neurosciences Abstracts
Nucleic Acids Abstracts
Oncogenes and Growth Factors Abstracts
Virology and AIDS Abstracts
Technology Research Database
Environmental Sciences and Pollution Management
Engineering Research Database
AIDS and Cancer Research Abstracts
Algology Mycology and Protozoology Abstracts (Microbiology C)
Biotechnology and BioEngineering Abstracts
Genetics Abstracts
MEDLINE - Academic
PubMed Central (Full Participant titles)
SwePub
SwePub Articles
SWEPUB Uppsala universitet
DatabaseTitle MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
CrossRef
Virology and AIDS Abstracts
Oncogenes and Growth Factors Abstracts
Technology Research Database
Nucleic Acids Abstracts
Ecology Abstracts
Neurosciences Abstracts
Biotechnology and BioEngineering Abstracts
Environmental Sciences and Pollution Management
Entomology Abstracts
Genetics Abstracts
Animal Behavior Abstracts
Bacteriology Abstracts (Microbiology B)
Algology Mycology and Protozoology Abstracts (Microbiology C)
AIDS and Cancer Research Abstracts
Chemoreception Abstracts
Immunology Abstracts
Engineering Research Database
Calcium & Calcified Tissue Abstracts
MEDLINE - Academic
DatabaseTitleList



MEDLINE
Virology and AIDS Abstracts
Neurosciences Abstracts
CrossRef
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
– sequence: 3
  dbid: FBQ
  name: AGRIS
  url: http://www.fao.org/agris/Centre.asp?Menu_1ID=DB&Menu_2ID=DB1&Language=EN&Content=http://www.fao.org/agris/search?Language=EN
  sourceTypes: Publisher
DeliveryMethod fulltext_linktorsrc
Discipline Sciences (General)
Medicine
EISSN 1091-6490
EndPage E401
ExternalDocumentID oai_DiVA_org_uu_157245
2418033451
10_1073_pnas_1101707108
21712437
108_31_E392
US201600192008
Genre Research Support, Non-U.S. Gov't
Journal Article
Feature
GroupedDBID ---
-DZ
-~X
.55
.GJ
0R~
123
29P
2AX
2FS
2WC
3O-
4.4
53G
5RE
5VS
692
6TJ
79B
85S
AACGO
AAFWJ
AANCE
AAYJJ
ABBHK
ABOCM
ABPLY
ABPPZ
ABPTK
ABTLG
ABZEH
ACGOD
ACIWK
ACKIV
ACNCT
ACPRK
ADULT
ADZLD
AENEX
AEUPB
AEXZC
AFDAS
AFFNX
AFOSN
AFRAH
ALMA_UNASSIGNED_HOLDINGS
ASUFR
AS~
BKOMP
CS3
D0L
DCCCD
DIK
DNJUQ
DOOOF
DU5
DWIUU
E3Z
EBS
EJD
F20
F5P
FBQ
FRP
GX1
HGD
HH5
HQ3
HTVGU
HYE
JAAYA
JBMMH
JENOY
JHFFW
JKQEH
JLS
JLXEF
JPM
JSG
JSODD
JST
KQ8
L7B
LU7
MVM
N9A
NEJ
NHB
N~3
O9-
OK1
P-O
PNE
PQQKQ
R.V
RHF
RHI
RNA
RNS
RPM
RXW
SA0
SJN
TAE
TN5
UKR
VOH
VQA
W8F
WH7
WHG
WOQ
WOW
X7M
XFK
XSW
Y6R
YBH
YKV
YSK
ZA5
ZCA
ZCG
~02
~KM
-
02
0R
1AW
55
AAPBV
ABFLS
ADACO
AJYGW
DZ
H13
KM
PQEST
X
XHC
ABXSQ
ADACV
AQVQM
CGR
CUY
CVF
ECM
EIF
IPSME
NPM
AAYXX
CITATION
7QG
7QL
7QP
7QR
7SN
7SS
7T5
7TK
7TM
7TO
7U9
8FD
C1K
FR3
H94
M7N
P64
RC3
7X8
ADQXQ
5PM
ADTPV
AOWAS
DF2
ID FETCH-LOGICAL-c603t-445306f84090db4980875e93f8a2ec4fa44890adfd8b80c98b0848b4c7ef4163
IEDL.DBID RPM
ISSN 0027-8424
1091-6490
IngestDate Sat Aug 24 00:35:13 EDT 2024
Tue Sep 17 21:14:32 EDT 2024
Fri Aug 16 02:05:17 EDT 2024
Sat Aug 17 00:58:59 EDT 2024
Thu Oct 10 17:52:10 EDT 2024
Fri Aug 23 01:10:26 EDT 2024
Sat Sep 28 07:48:49 EDT 2024
Wed Nov 11 00:29:38 EST 2020
Wed Dec 27 18:57:59 EST 2023
IsDoiOpenAccess false
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 31
Language English
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c603t-445306f84090db4980875e93f8a2ec4fa44890adfd8b80c98b0848b4c7ef4163
Notes http://dx.doi.org/10.1073/pnas.1101707108
ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
ObjectType-Article-1
ObjectType-Feature-2
Author contributions: M.W.K. designed research; C.L., M.M.L., X.W., B.H., N.T., and G.H. performed research; C.L., M.M.L., and M.W.K. analyzed data; and M.W.K. wrote the paper.
1Present address: Robert Koch-Institut, D-13353 Berlin, Germany.
Edited by Nils Brose, Max Planck Institute for Experimental Medicine, Göttingen, Germany, and accepted by the Editorial Board June 7, 2011 (received for review January 30, 2011)
2Present address: Evotec NeuroScience, D-22525 Hamburg, Germany.
OpenAccessLink https://www.pnas.org/content/pnas/108/31/E392.full.pdf
PMID 21712437
PQID 881298321
PQPubID 42026
ParticipantIDs proquest_miscellaneous_881087406
proquest_miscellaneous_1093461330
pnas_primary_108_31_E392
crossref_primary_10_1073_pnas_1101707108
proquest_journals_881298321
fao_agris_US201600192008
swepub_primary_oai_DiVA_org_uu_157245
pubmedcentral_primary_oai_pubmedcentral_nih_gov_3150911
pubmed_primary_21712437
ProviderPackageCode RNA
PNE
PublicationCentury 2000
PublicationDate 2011-08-02
PublicationDateYYYYMMDD 2011-08-02
PublicationDate_xml – month: 08
  year: 2011
  text: 2011-08-02
  day: 02
PublicationDecade 2010
PublicationPlace United States
PublicationPlace_xml – name: United States
– name: Washington
PublicationSeriesTitle PNAS Plus
PublicationTitle Proceedings of the National Academy of Sciences - PNAS
PublicationTitleAlternate Proc Natl Acad Sci U S A
PublicationYear 2011
Publisher National Academy of Sciences
National Acad Sciences
Publisher_xml – name: National Academy of Sciences
– name: National Acad Sciences
References 20065095 - J Cell Biol. 2010 Jan 11;188(1):145-56
2027472 - Neuroscience. 1991;40(2):587-98
18417694 - J Neurosci. 2008 Apr 16;28(16):4151-60
19812333 - J Neurosci. 2009 Oct 7;29(40):12584-96
21144999 - Neuron. 2010 Dec 9;68(5):843-56
10707984 - Neuron. 2000 Jan;25(1):203-14
15728193 - J Cell Biol. 2005 Feb 28;168(5):825-36
18005987 - J Mol Biol. 2008 Jan 4;375(1):217-28
17197287 - Prog Histochem Cytochem. 2007;41(3):141-200
10944438 - Biochem Biophys Res Commun. 2000 Aug 18;275(1):43-6
20332206 - Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6504-9
11438518 - J Biol Chem. 2001 Aug 31;276(35):32756-62
2536030 - J Cell Biol. 1989 Jan;108(1):111-26
1453003 - J Histochem Cytochem. 1992 Dec;40(12):1849-56
19067356 - J Comp Neurol. 2009 Feb 20;512(6):814-24
16485285 - J Comp Neurol. 2006 Apr 1;495(4):480-96
19596851 - J Cell Biol. 2009 Jul 13;186(1):129-45
11596050 - J Comp Neurol. 2001 Oct 15;439(2):224-34
17610814 - Neuron. 2007 Jul 5;55(1):11-24
18588488 - Annu Rev Cell Dev Biol. 2008;24:237-62
18519737 - J Cell Biol. 2008 Jun 2;181(5):831-46
19874790 - Neuron. 2009 Oct 29;64(2):227-39
21092860 - Neuron. 2010 Nov 18;68(4):710-23
19226520 - J Comp Neurol. 2009 Apr 10;513(5):457-68
12628168 - Neuron. 2003 Mar 6;37(5):775-86
1709656 - J Histochem Cytochem. 1991 Jun;39(6):741-8
11259787 - Brain Res. 2001 Mar 23;895(1-2):258-63
10564375 - Eur J Neurosci. 1999 Oct;11(10):3683-93
15381754 - Physiology (Bethesda). 2004 Oct;19:262-70
4173151 - J Ultrastruct Res. 1968 Mar;22(5):361-75
6181433 - Neuroscience. 1982 Jul;7(7):1779-83
17596435 - J Neurosci. 2007 Jun 27;27(26):6868-77
3531521 - J Microsc. 1986 Jul;143(Pt 1):81-8
16942804 - Trends Neurosci. 2006 Nov;29(11):617-24
11604139 - Neuron. 2001 Oct 11;32(1):63-77
20980589 - J Neurosci. 2010 Oct 27;30(43):14340-5
15066152 - Eur J Neurosci. 2004 Mar;19(6):1559-71
11206537 - Nature. 2001 Jan 25;409(6819):479-84
3152289 - Neuron. 1988 May;1(3):201-9
12575947 - Neuron. 2003 Feb 6;37(3):379-82
6167611 - J Histochem Cytochem. 1981 Jul;29(7):844-50
10508862 - J Cell Biol. 1999 Oct 4;147(1):151-62
16757121 - Neuroscience. 2006 Sep 1;141(3):1217-24
9697857 - Neuron. 1998 Jul;21(1):123-36
16865347 - Cell Tissue Res. 2006 Nov;326(2):379-91
19074017 - J Neurosci. 2008 Dec 10;28(50):13435-47
19154334 - J Neurochem. 2009 Mar;108(6):1336-42
1707044 - Histochemistry. 1990;95(2):123-36
e_1_3_3_50_2
e_1_1_2_17_10_4_2
e_1_1_2_17_10_2_2
e_1_3_3_16_2
e_1_3_3_18_2
e_1_3_3_39_2
e_1_3_3_12_2
e_1_3_3_37_2
e_1_3_3_14_2
e_1_3_3_35_2
e_1_3_3_33_2
e_1_3_3_10_2
e_1_3_3_31_2
e_1_3_3_40_2
e_1_3_3_5_2
e_1_3_3_7_2
e_1_3_3_9_2
e_1_3_3_27_2
e_1_3_3_29_2
e_1_3_3_23_2
e_1_3_3_48_2
e_1_3_3_25_2
e_1_3_3_46_2
e_1_3_3_1_2
e_1_3_3_44_2
e_1_3_3_3_2
e_1_3_3_21_2
e_1_3_3_42_2
Harris JR (e_1_3_3_22_2) 1991
e_1_1_2_17_10_5_2
e_1_1_2_17_10_3_2
e_1_1_2_17_10_1_2
e_1_3_3_17_2
e_1_3_3_19_2
e_1_3_3_38_2
e_1_3_3_13_2
e_1_3_3_36_2
e_1_3_3_15_2
e_1_3_3_34_2
e_1_3_3_32_2
e_1_3_3_11_2
e_1_3_3_30_2
e_1_3_3_6_2
e_1_3_3_8_2
e_1_3_3_28_2
e_1_3_3_49_2
e_1_3_3_24_2
e_1_3_3_47_2
e_1_3_3_26_2
e_1_3_3_45_2
e_1_3_3_2_2
e_1_3_3_20_2
e_1_3_3_43_2
e_1_3_3_4_2
e_1_3_3_41_2
References_xml – ident: e_1_3_3_10_2
  doi: 10.1007/BF00266584
– ident: e_1_3_3_49_2
  doi: 10.1016/j.proghi.2006.09.001
– ident: e_1_3_3_41_2
  doi: 10.1002/cne.20893
– ident: e_1_1_2_17_10_3_2
  doi: 10.1523/JNEUROSCI.1255-09.2009
– ident: e_1_3_3_40_2
  doi: 10.1002/cne.1344
– ident: e_1_3_3_39_2
  doi: 10.1046/j.1460-9568.1999.00793.x
– ident: e_1_3_3_46_2
  doi: 10.1111/j.1365-2818.1986.tb02766.x
– ident: e_1_1_2_17_10_4_2
  doi: 10.1083/jcb.200711167
– ident: e_1_1_2_17_10_2_2
  doi: 10.1016/S0022-5320(68)90027-0
– ident: e_1_3_3_25_2
  doi: 10.1083/jcb.200408157
– ident: e_1_3_3_5_2
  doi: 10.1523/JNEUROSCI.1255-09.2009
– ident: e_1_3_3_31_2
  doi: 10.1002/cne.21915
– ident: e_1_3_3_37_2
  doi: 10.1016/j.tins.2006.08.006
– ident: e_1_3_3_24_2
  doi: 10.1016/j.jmb.2007.10.029
– ident: e_1_3_3_34_2
  doi: 10.1016/j.neuroscience.2006.04.061
– ident: e_1_3_3_42_2
  doi: 10.1016/S0006-8993(01)02078-9
– ident: e_1_3_3_43_2
  doi: 10.1523/JNEUROSCI.3235-08.2008
– ident: e_1_3_3_48_2
  doi: 10.1177/39.6.1709656
– ident: e_1_3_3_18_2
  doi: 10.1083/jcb.200908082
– ident: e_1_3_3_2_2
  doi: 10.1007/s00441-006-0244-y
– ident: e_1_3_3_13_2
  doi: 10.1523/JNEUROSCI.4639-07.2008
– ident: e_1_3_3_17_2
  doi: 10.1111/j.1471-4159.2009.05888.x
– ident: e_1_3_3_6_2
  doi: 10.1083/jcb.147.1.151
– ident: e_1_3_3_32_2
  doi: 10.1006/bbrc.2000.3256
– ident: e_1_3_3_12_2
  doi: 10.1111/j.1460-9568.2004.03198.x
– ident: e_1_3_3_20_2
  doi: 10.1083/jcb.108.1.111
– ident: e_1_3_3_45_2
  doi: 10.1177/29.7.6167611
– ident: e_1_3_3_8_2
  doi: 10.1146/annurev.cellbio.23.090506.123417
– ident: e_1_3_3_7_2
  doi: 10.1016/S0896-6273(00)80883-1
– ident: e_1_3_3_9_2
  doi: 10.1016/j.neuron.2009.09.019
– ident: e_1_1_2_17_10_1_2
  doi: 10.1007/s00441-006-0244-y
– ident: e_1_3_3_16_2
  doi: 10.1523/JNEUROSCI.1773-07.2007
– ident: e_1_1_2_17_10_5_2
  doi: 10.1073/pnas.1002307107
– ident: e_1_3_3_1_2
  doi: 10.1016/j.neuron.2007.06.013
– ident: e_1_3_3_4_2
  doi: 10.1152/physiol.00014.2004
– start-page: 203
  volume-title: Electron Microscopy in Biology: A Practical Approach
  year: 1991
  ident: e_1_3_3_22_2
  doi: 10.1093/oso/9780199632190.003.0009
  contributor:
    fullname: Harris JR
– ident: e_1_3_3_28_2
  doi: 10.1016/j.neuron.2010.10.026
– ident: e_1_3_3_19_2
  doi: 10.1016/0896-6273(88)90140-7
– ident: e_1_3_3_33_2
  doi: 10.1016/j.neuron.2010.11.021
– ident: e_1_3_3_36_2
  doi: 10.1074/jbc.M100929200
– ident: e_1_3_3_35_2
  doi: 10.1016/S0896-6273(00)80520-6
– ident: e_1_3_3_21_2
  doi: 10.1016/0306-4522(91)90143-C
– ident: e_1_3_3_3_2
  doi: 10.1016/S0896-6273(01)00450-0
– ident: e_1_3_3_14_2
  doi: 10.1038/35054000
– ident: e_1_3_3_27_2
  doi: 10.1073/pnas.1002307107
– ident: e_1_3_3_29_2
  doi: 10.1523/JNEUROSCI.2495-10.2010
– ident: e_1_3_3_11_2
  doi: 10.1016/S0022-5320(68)90027-0
– ident: e_1_3_3_44_2
  doi: 10.1016/0306-4522(82)90035-5
– ident: e_1_3_3_30_2
  doi: 10.1016/S0896-6273(03)00062-X
– ident: e_1_3_3_50_2
  doi: 10.1007/978-1-4684-0123-3_4
– ident: e_1_3_3_38_2
  doi: 10.1016/S0896-6273(03)00086-2
– ident: e_1_3_3_15_2
  doi: 10.1002/cne.21975
– ident: e_1_3_3_47_2
  doi: 10.1177/40.12.1453003
– ident: e_1_3_3_26_2
  doi: 10.1083/jcb.200711167
– ident: e_1_3_3_23_2
  doi: 10.1083/jcb.200812150
SSID ssj0009580
Score 2.3201404
Snippet The protein machinery of neurotransmitter exocytosis requires efficient orchestration in space and time, for speed and precision of neurotransmission and also...
SourceID swepub
pubmedcentral
proquest
crossref
pubmed
pnas
fao
SourceType Open Access Repository
Aggregation Database
Index Database
Publisher
StartPage E392
SubjectTerms Adaptor Proteins, Signal Transducing - metabolism
Animals
Binding Sites
Biological Sciences
Cell Membrane - metabolism
Cell Membrane - ultrastructure
Cytoskeletal Proteins - metabolism
electron microscopy
exocytosis
GTP-Binding Proteins - metabolism
Immunoblotting
Mammals
MEDICIN
MEDICINE
Membranes
Microscopy, Immunoelectron
Molecular structure
Multiprotein Complexes - metabolism
Multiprotein Complexes - ultrastructure
Nerve Tissue Proteins - metabolism
Neuropeptides - metabolism
Neurotransmitter Agents - metabolism
Neurotransmitters
ontogeny
plasma membrane
PNAS Plus
polypeptides
Protein Binding
protein structure
Proteins
Rats
Rats, Sprague-Dawley
scaffolding protein
space and time
Synapses - metabolism
Synapses - ultrastructure
synaptic transmission
topology
Title Molecular in situ topology of Aczonin/Piccolo and associated proteins at the mammalian neurotransmitter release site
URI http://www.pnas.org/content/108/31/E392.abstract
https://www.ncbi.nlm.nih.gov/pubmed/21712437
https://www.proquest.com/docview/881298321
https://search.proquest.com/docview/1093461330
https://search.proquest.com/docview/881087406
https://pubmed.ncbi.nlm.nih.gov/PMC3150911
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-157245
Volume 108
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Nb9QwEB11e-KCKF8NhcpIIJXDdpPY2STHVWlVQIsq0aLeLCex20jEWTXJgf76zjjJVhFw4ZKLHdvyjD1v7PEbgA95IXBjNBTwFCznqBTufhcFotFcR1mCHzqHXH9fnl-Jr9fR9Q5E41sYF7SfZ-Wx_VUd2_LWxVZuqnwxxoktLtYnPCAzFyxmMIs5H130LdNu0r87CXH7FaEY-XxivthY1VDcexCTYU0cEXAcECXfxCrNjKqJ6xRr_w13_hk-OSEZdYbp7Bk8HRAlW_Uj34MdbZ_D3rBmG3Y0EEt_egHtesyFy0rLmrLtWNvnSPjNasNW-T2dzS4uypyorJmyBVOD9HTBHKNDaRumWoaokVWqqtwhCXOcmC0Zvaqkx0GMErGgdaQu9Eu4PDu9PDmfD1kX5vnS5-1ciAjdCEOOn19kIk2I816n3CQq1LkwCh261FeFKZIs8fM0yYiSPxN5rA2hu1ewa2ur94EVpB6GXEIUA5Hw6CjIeGx0HGZFblIPjsZJl5ueW0O6O_GYS5p8-SgqD_ZRKFLd4M4nr36ExItH4NR3Ra7yYwuJ5IE8ReDnwcEoPTkszUYmCGlSys_kwfttKa4puihRVtddQ7fyXCDO4b4H7B91sBmf0hkuPXjdq8N2BKNSeRBPFGVbgSi9pyWo6Y7ae9BsDz72KjX55XP5cyXruxvZdTKI4lBEb_67hwN4Mp6O--Fb2G3vOv0O4VWbHaJj8eXboVtUDz38Iws
link.rule.ids 230,315,733,786,790,891,27955,27956,53825,53827
linkProvider National Library of Medicine
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lb9QwEB615QAXoLwaysNIIJXDbl7OJjmuSqsFulUltlVvluPYJYJkV01yoL-eGSfZankc4JKLnZfms-cbe_wNwFuVc5wYDSU8-ZMRgsLu76JBNLrrKEvwQuuQ89PJ7Jx_uowutyAazsLYpH2VFePqezmuiq82t3JVKnfIE3PP5oehT27Od7fhDo7XIBqC9LXWbtKdPAlwAuYBHxR94tBdVbKmzHc_JteaWCng2CdRvg2_tG3kktROsfefmOfvCZQbMqPWNR0_gIvhp7qMlG_jtsnG6uYXvcd__uuHcL8nq2zaNe_Clq4ewW4_HdTsoNesfv8YmvlQZpcVFauLpmVNV37hB1saNlU3tOzrnhWKVLKZrHIme2DonFmxiKKqmWwYElJWyrK06y_Mym025E_Lgs4dMarxgo6XXqGfwOL4aHE4G_UFHUZq4oXNiPMIIxRDMaWXZzxNSE5fp6FJZKAVNxJjxdSTucmTLPFUmmSk9p9xFWtDxPEp7FTLSu8Bywl5hqJNtC_p--jIz8LY6DjIcmVSBw4Ga4pVJ9sh7HZ7HAqyqrjFgAN7aG0hr3BSFedfApLcI97r2Sbb-fYJiQh9cYSc0oH9ARaiH_W1SJAtpVT6yYE361YcrrQHIyu9bGva8A85UqjQc4D9pQ8-xqNKiRMHnnU4W3_BgFYH4g0ErjuQWvhmC8LJqob38HHgXYfVjVs-FBdTsby-Em0r_CgOePT8v9_wGu7OFvMTcfLx9PM-3BsW4b3gBew0161-iSyuyV7ZMfsTXuVD_A
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lb9QwEB7RIiEuQHk1lIeRQCqH3bycTXJctV2Vx1Yr0aKKi-U4dokg2VWTHOivZ8ZJtiyPSy978STZaD57vrEn3wC8UTnHhdFQwZM_GSEo7PkuOkRjuI6yBH9oH3J-Mjk-4x_Oo_PfWn3Zon2VFePqRzmuim-2tnJVKneoE3MX84PQpzDnu6vcuFtwG-dsEA-J-lpvN-m-PglwEeYBH1R94tBdVbKm6nc_pvCaWDng2Cdhvo3YtGXkkhRP0fpf7PPvIsoNqVEbnmb34evwYl1Vyvdx22RjdfWH5uON3vwB3OtJK5t2JjtwS1cPYadfFmq232tXv3sEzXxot8uKitVF07Kma8Pwky0Nm6or2v51F4UitWwmq5zJHiA6Z1Y0oqhqJhuGxJSVsiztPgyzspsNxdWyoO-PGPV6wQBMj9CP4XR2dHpwPOobO4zUxAubEecRZiqGcksvz3iakKy-TkOTyEArbiTmjKknc5MnWeKpNMlI9T_jKtaGCOQT2K6Wld4FlhMCDWWd6GPS-dGRn4Wx0XGQ5cqkDuwPHhWrTr5D2GP3OBTkWXGNAwd20eNCXuDiKs4-ByS9R_zXs0PW-PoOiQh9cYTc0oG9ARqin_21SJA1pdQCyoHX61GctnQWIyu9bGs6-A85UqnQc4D9xwZv41HHxIkDTzusrf_BgFgH4g0Urg1INXxzBCFl1cN7CDnwtsPrxiWHxZepWF5eiLYVfhQHPHp24ye8gjuLw5n49P7k4x7cHfbiveA5bDeXrX6BZK7JXtpp-wt1FkZ8
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Molecular+in+situ+topology+of+Aczonin%2FPiccolo+and+associated+proteins+at+the+mammalian+neurotransmitter+release+site&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+-+PNAS&rft.au=Limbach%2C+Christoph&rft.au=Laue%2C+Michael+M.&rft.au=Wang%2C+Xiaolu&rft.au=Hu%2C+Bin&rft.date=2011-08-02&rft.issn=0027-8424&rft.volume=108&rft.issue=31&rft.spage=E392&rft_id=info:doi/10.1073%2Fpnas.1101707108&rft.externalDocID=oai_DiVA_org_uu_157245
thumbnail_m http://utb.summon.serialssolutions.com/2.0.0/image/custom?url=http%3A%2F%2Fwww.pnas.org%2Fcontent%2F108%2F31.cover.gif
thumbnail_s http://utb.summon.serialssolutions.com/2.0.0/image/custom?url=http%3A%2F%2Fwww.pnas.org%2Fcontent%2F108%2F31.cover.gif