Document Detail

Presenilin/gamma-secretase cleaves CD46 in response to Neisseria infection.
MedLine Citation:
PMID:  20018629     Owner:  NLM     Status:  MEDLINE    
CD46 is a type I transmembrane protein with complement and T cell regulatory functions in human cells. CD46 has signaling and receptor properties in immune and nonimmune cells, many of which are dependent on the expression of cytoplasmic tail (cyt) isoforms cyt1 or cyt2. Little is known about how cyt1 and cyt2 mediate cellular responses. We show that CD46-cyt1 and CD46-cyt2 are substrates for presenilin/gamma-secretase (PS/gammaS), an endogenous protease complex that regulates many important signaling proteins through proteolytic processing. PS/gammaS processing of CD46 releases immunoprecipitable cyt1 and cyt2 tail peptides into the cell, is blocked by chemical inhibitors, and is prevented in dominant negative presenilin mutant cell lines. Two human pathogens, Neisseria gonorrhoeae and Neisseria meningitidis, stimulate PS/gammaS processing of CD46-cyt1 and CD46-cyt2. This stimulation requires type IV pili and PilT, the type IV pilus retraction motor, implying that mechanotransduction plays a role in this event. We present a model for PS/gammaS processing of CD46 that provides a mechanism by which signals are transduced via the cyt1 and cyt2 tails to regulate CD46-dependent cellular responses. Our findings have broad implications for understanding the full range of CD46 functions in infection and noninfection situations.
Nathan J Weyand; Christine M Calton; Dustin L Higashi; Kristen J Kanack; Magdalene So
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-12-16
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  184     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-01-07     Completed Date:  2010-02-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  694-701     Citation Subset:  AIM; IM    
BIO5 Institute, University of Arizona, Tucson, AZ 85721, USA.
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MeSH Terms
Amyloid Precursor Protein Secretases / metabolism*
Antigens, CD46 / metabolism*,  physiology
Fimbriae, Bacterial
Gonorrhea / metabolism*
Mechanotransduction, Cellular
Meningococcal Infections / metabolism*
Neisseria gonorrhoeae
Neisseria meningitidis
Presenilins / metabolism*
Protein Isoforms
Signal Transduction
Grant Support
Reg. No./Substance:
0/Antigens, CD46; 0/Presenilins; 0/Protein Isoforms; EC 3.4.-/Amyloid Precursor Protein Secretases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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