Conformational Defects Slow Golgi Exit, Block Oligomerization, and Reduce Raft Affinity of Caveolin-1 Mutant Proteins
10.1091/mbc.e04-06-0480
Crossref journal-article
American Society for Cell Biology (ASCB)
Molecular Biology of the Cell (1076)
Abstract

Caveolin-1, a structural protein of caveolae, is cleared unusually slowly from the Golgi apparatus during biosynthetic transport. Furthermore, several caveolin-1 mutant proteins accumulate in the Golgi apparatus. We examined this behavior further in this mutant study. Golgi accumulation probably resulted from loss of Golgi exit information, not exposure of cryptic retention signals, because several deletion mutants accumulated in the Golgi apparatus. Alterations throughout the protein caused Golgi accumulation. Thus, most probably acted indirectly, by affecting overall conformation, rather than by disrupting specific Golgi exit motifs. Consistent with this idea, almost all the Golgi-localized mutant proteins failed to oligomerize normally (even with an intact oligomerization domain), and they showed reduced raft affinity in an in vitro detergent-insolubility assay. A few mutant proteins formed unstable oligomers that migrated unusually slowly on blue native gels. Only one mutant protein, which lacked the first half of the N-terminal hydrophilic domain, accumulated in the Golgi apparatus despite normal oligomerization and raft association. These results suggested that transport of caveolin-1 through the Golgi apparatus is unusually difficult. The conformation of caveolin-1 may be optimized to overcome this difficulty, but remain very sensitive to mutation. Disrupting conformation can coordinately affect oligomerization, raft affinity, and Golgi exit of caveolin-1.

Bibliography

Ren, X., Ostermeyer, A. G., Ramcharan, L. T., Zeng, Y., Lublin, D. M., & Brown, D. A. (2004). Conformational Defects Slow Golgi Exit, Block Oligomerization, and Reduce Raft Affinity of Caveolin-1 Mutant Proteins. Molecular Biology of the Cell, 15(10), 4556–4567.

Authors 6
  1. Xiaoyan Ren (first)
  2. Anne G. Ostermeyer (additional)
  3. Lynne T. Ramcharan (additional)
  4. Youchun Zeng (additional)
  5. Douglas M. Lublin (additional)
  6. Deborah A. Brown (additional)
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Dates
Type When
Created 21 years ago (Aug. 10, 2004, 9:23 p.m.)
Deposited 4 years, 2 months ago (June 24, 2021, 6:56 p.m.)
Indexed 1 year, 2 months ago (July 5, 2024, 11:15 a.m.)
Issued 20 years, 11 months ago (Oct. 1, 2004)
Published 20 years, 11 months ago (Oct. 1, 2004)
Published Print 20 years, 11 months ago (Oct. 1, 2004)
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@article{Ren_2004, title={Conformational Defects Slow Golgi Exit, Block Oligomerization, and Reduce Raft Affinity of Caveolin-1 Mutant Proteins}, volume={15}, ISSN={1939-4586}, url={http://dx.doi.org/10.1091/mbc.e04-06-0480}, DOI={10.1091/mbc.e04-06-0480}, number={10}, journal={Molecular Biology of the Cell}, publisher={American Society for Cell Biology (ASCB)}, author={Ren, Xiaoyan and Ostermeyer, Anne G. and Ramcharan, Lynne T. and Zeng, Youchun and Lublin, Douglas M. and Brown, Deborah A.}, year={2004}, month=oct, pages={4556–4567} }