Subsynaptic positioning of AMPARs by LRRTM2 controls synaptic strength
The nanoscale distribution of AMPA receptors is under rapid control by adhesion proteins and helps regulate their activation. Recent evidence suggests that nano-organization of proteins within synapses may control the strength of communication between neurons in the brain. The unique subsynaptic dis...
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Published in | Science advances Vol. 7; no. 34 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
American Association for the Advancement of Science
20.08.2021
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Subjects | |
Online Access | Get full text |
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Summary: | The nanoscale distribution of AMPA receptors is under rapid control by adhesion proteins and helps regulate their activation.
Recent evidence suggests that nano-organization of proteins within synapses may control the strength of communication between neurons in the brain. The unique subsynaptic distribution of glutamate receptors, which cluster in nanoalignment with presynaptic sites of glutamate release, supports this hypothesis. However, testing it has been difficult because mechanisms controlling subsynaptic organization remain unknown. Reasoning that transcellular interactions could position AMPA receptors (AMPARs), we targeted a key transsynaptic adhesion molecule implicated in controlling AMPAR number, LRRTM2, using engineered, rapid proteolysis. Severing the LRRTM2 extracellular domain led quickly to nanoscale declustering of AMPARs away from release sites, not prompting their escape from synapses until much later. This rapid remodeling of AMPAR position produced significant deficits in evoked, but not spontaneous, postsynaptic receptor activation. These results dissociate receptor numbers from their nanopositioning in determination of synaptic function and support the novel concept that adhesion molecules acutely position receptors to dynamically control synaptic strength. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Present address: CAS Key Laboratory of Brain Function and Disease and Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. These authors contributed equally to this work. Present address: Ohio State University College of Medicine, Columbus, OH, USA. Present address: Department of Biological Sciences, University of Maryland, Baltimore County, Baltimore, MD, USA. |
ISSN: | 2375-2548 2375-2548 |
DOI: | 10.1126/sciadv.abf3126 |