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PrP octarepeats region determined the interaction with caveolin-1 and phosphorylation of caveolin-1 and Fyn.
MedLine Citation:
PMID:  23283514     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Caveolin-1 is one of the major constituents of caveolae. Both Cav-1 and PrP are plasma membrane proteins, which show active capacities for molecular interactions with many other proteins or agents, including themselves. Using yeast two-hybrid system and immunoprecipitation, we reconfirmed the molecular interaction between human Cav-1 and PrP. With co-immunoprecipitation tests, PrP(C)-Cav-1 and PrP(Sc)-Cav-1 complexes were identified in the brain homogenates of normal and scrapie agent 263K-infected hamsters, respectively. Transient expression of wild-type PrP (PrP-PG5) in HEK293 cells did not change the situation of Cav-1 and subsequent signal transduction pathways, while cross-linking of the expressed PrP with specific antibody induced remarkable colocalization of PrP and Cav-1 on the plasma membrane and significant increases of phosphorylated Cav-1 and phosphorylated Fyn. With deleted and inserted PrP mutants within octarepeat region, we observed obvious octarepeat-associated phenomena, including lower binding capacity with Cav-1 in vitro, unable to co-localize with Cav-1 in the cells and to induce up-regulation of p-Cav-1 and p-Fyn when removal of octarepeats in the context of full-length PrP. Moreover, we found that treatment on HEK293 cells with fibrous form of recombinant PrP protein led to up-regulating the levels of p-Cav-1 and p-Fyn. Our data here provide strong evidence that octarepeats of PrP are critical for the interaction between PrP and Cav-1. Significant alterations in the cultured cells, either the distributions of PrP and Cav-1 morphologically or the up-regulations of p-Cav-1 and p-Fyn, induced by antibody-mediated cross-linking or fibrous forms of PrP may suggest a possible internalization process of PrP(Sc).
Authors:
Qi Shi; Yuan-Yuan Jing; Shao-Bin Wang; Cao Chen; Han Sun; Yin Xu; Chen Gao; Jin Zhang; Chan Tian; Yan Guo; Ke Ren; Xiao-Ping Dong
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-3
Journal Detail:
Title:  Medical microbiology and immunology     Volume:  -     ISSN:  1432-1831     ISO Abbreviation:  Med. Microbiol. Immunol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0314524     Medline TA:  Med Microbiol Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, People's Republic of China.
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