The presenilin (PS)/γ-secretase complex proteolytically cleaves more than 20 different proteins in addition to the amyloid precursor protein (APP). These substrates are almost exclusively type I membrane proteins. Many undergo internalization from the cell surface followed by degradation or recycling back to the plasma membrane through the endocytic recycling compartment (ERC). Evidence shows that the PSs also regulate intracellular trafficking of APP and its C-terminal fragments (CTFs). To investigate whether PS/γ-secretase activity is required for normal endosomal recycling, we performed live cell imaging experiments with fluorescently labeled transferrin, reported to specifically traffic through the ERC. By using pharmacological γ-secretase inhibitors or cell lines lacking functional PS/γ-secretase, here we show that PS/γ-secretase activity is required for clearance of transferrin from the ERC. Interestingly, lack of PS/γ-secretase function also resulted in the accumulation of APP and APP-CTFs in the ERC in addition to the cell surface. Familial Alzheimer’s disease mutations in APP-CTFs did not affect endocytic recycling of these proteins. Our results suggest that PS/γ-secretase activity is required for normal endosomal recycling of soluble and membrane-associated proteins through the ERC and propose a new mechanism by which impaired PS/γ-secretase function may eventually contribute to neurodegeneration.—Zhang, M., Haapasalo, A., Kim, D. Y., MacKenzie Ingano, L. A., Pettingell, W. H., and Kovacs, D. M. Presenilin/γ-secretase activity regulates protein clearance from the endocytic recycling compartment.
End of preview. The entire article is 13 pages. To view the full-text, please rent this article to continue.
/lp/fed-of-american-socs-for-experimental-biology/presenilin-secretase-activity-regulates-protein-clearance-from-the-UQZDAFmZ4m
Welcome to DeepDyve! Rent Premier Research Articles and Save Up to 90%
Presenilin/γ-secretase activity regulates protein clearance from the endocytic recycling compartment
Zhang, Mei; Haapasalo, Annakaisa; Kim, Doo Yeon; Ingano, Laura A. MacKenzie; Pettingell, Warren H.; Kovacs, Dora M.
Follow The FASEB Journal
, Volume 20 (8): 1176
Fed of American Socs for Experimental Biology – Jun 1, 2006
More Info
More Like This Article
View All dataSource[]=actageo&dataSource[]=aspet&dataSource[]=aaos&dataSource[]=aacc&dataSource[]=aacr&dataSource[]=aea&dataSource[]=aip&dataSource[]=ajnr&dataSource[]=ams&dataSource[]=aps_physical&dataSource[]=appi_book&dataSource[]=appi_journal&dataSource[]=apha&dataSource[]=asip&dataSource[]=asm&dataSource[]=asn&dataSource[]=aspb&dataSource[]=avs&dataSource[]=annual_reviews&dataSource[]=arxiv&dataSource[]=acm&dataSource[]=berghahn&dataSource[]=cabi&dataSource[]=clinical_trials&dataSource[]=dailymed&dataSource[]=degruyter&dataSource[]=du_press&dataSource[]=esa&dataSource[]=eu_press&dataSource[]=elsevier&dataSource[]=emerald&dataSource[]=ejtr&dataSource[]=emea&dataSource[]=epo&dataSource[]=faseb&dataSource[]=gsa&dataSource[]=health_affairs&dataSource[]=hindawi&dataSource[]=imanager&dataSource[]=imedpub&dataSource[]=informa_healthcare&dataSource[]=informs&dataSource[]=iop&dataSource[]=iucr&dataSource[]=iospress&dataSource[]=jbjs&dataSource[]=leftcoast&dataSource[]=lu_press&dataSource[]=mesharpe&dataSource[]=mary_ann_liebert&dataSource[]=medline&dataSource[]=mit_press&dataSource[]=nature&dataSource[]=oxford&dataSource[]=pier_professional&dataSource[]=pnas&dataSource[]=portlandpress&dataSource[]=psyc_articles&dataSource[]=psyc_books&dataSource[]=psyc_critiques&dataSource[]=plos_journal&dataSource[]=pubmed_central&dataSource[]=rsna&dataSource[]=rockefeller&dataSource[]=rcn&dataSource[]=ria&dataSource[]=rsc&dataSource[]=sage&dataSource[]=spie&dataSource[]=springer_journal&dataSource[]=springer&dataSource[]=taylor_francis&dataSource[]=aps&dataSource[]=the_scientist&dataSource[]=uc_press&dataSource[]=uspto_abstract&dataSource[]=wiley&dataSource[]=pct
© 2012 DeepDyve, Inc. All rights reserved.
Terms of Service | Privacy Policy
