Regulation of Inducible Nitric Oxide Synthase by Aggresome Formation

Misfolding and aggregation of proteins play an important part in the pathogenesis of several genetic and degenerative diseases. Recent evidence suggests that cells have evolved a pathway that involves sequestration of aggregated proteins into specialized "holding stations" called aggresome...

Full description

Saved in:
Bibliographic Details
Published inProceedings of the National Academy of Sciences - PNAS Vol. 102; no. 13; pp. 4854 - 4859
Main Authors Kolodziejska, Katarzyna E., Burns, Alan R., Moore, Robert H., Stenoien, David L., Eissa, N. Tony, Snyder, Solomon H.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 29.03.2005
National Acad Sciences
Subjects
Animals
Antibodies
B lymphocytes
Biological Sciences
Cell lines
Cells
Cells, Cultured
Cytokines
Disease
Dyneins - metabolism
Enzymes
Fluorescence
Fluorescence Recovery After Photobleaching
Green Fluorescent Proteins
HEK293 cells
Humans
Image Processing, Computer-Assisted
Inclusion Bodies - drug effects
Inclusion Bodies - metabolism
Indoles
Leupeptins - pharmacology
Mice
Microscopy, Electron
Microtubule-Organizing Center - drug effects
Microtubule-Organizing Center - metabolism
Microtubules
Misfolded proteins
Nitric oxide
Nitric Oxide Synthase - metabolism
Nitric Oxide Synthase Type II
Nocodazole - pharmacology
Protein folding
Vimentin
Online AccessGet full text

Cover

More Information
Summary:Misfolding and aggregation of proteins play an important part in the pathogenesis of several genetic and degenerative diseases. Recent evidence suggests that cells have evolved a pathway that involves sequestration of aggregated proteins into specialized "holding stations" called aggresomes. Here we show that cells regulate inducible NO synthase (iNOS), an important host defense protein, through aggresome formation. iNOS aggresome formation depends on a functional dynein motor and the integrity of the microtubules. The iNOS aggresome represents a "physiologic aggresome" and thus defines a new paradigm for cellular regulation of protein processing. This study indicates that aggresome formation in response to misfolded proteins may merely represent an acceleration of an established physiologic regulatory process for specific proteins whose regulation by aggresome formation is deemed necessary by the cell.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
ObjectType-Article-1
ObjectType-Feature-2
Author contributions: K.E.K., A.R.B., R.H.M., D.L.S., and N.T.E. designed research; K.E.K., A.R.B., and D.L.S. performed research; K.E.K., A.R.B., R.H.M., and N.T.E. analyzed data; and K.E.K., A.R.B., and N.T.E. wrote the paper.
Present address: Pacific Northwest National Laboratory, Richland, WA 99352.
Edited by Solomon H. Snyder, Johns Hopkins University School of Medicine, Baltimore, MD, and approved February 15, 2005
This paper was submitted directly (Track II) to the PNAS office.
To whom correspondence should be addressed. E-mail: teissa@bcm.tmc.edu.
Abbreviations: iNOS, inducible NO synthase; HEK, human embryonic kidney; DIC, Normaski differential interference contrast; MTOC, microtubule-organizing center.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0500485102