Document Detail


Homers regulate calcium entry and aggregation in human platelets. A role for Homers in the association between STIM1 and Orai1.
MedLine Citation:
PMID:  22506990     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Homer is a family of cytoplasmic adaptor proteins that plays different roles in cell function, including the regulation of G protein-coupled receptors. These proteins contain an Ena/VASP homology 1 domain that binds to the PPXXF sequence motif, which is present in different Ca2+-handling proteins such as IP3 receptors and TRPC channels. Here we present evidence for a role of Homer proteins in the STIM1/Orai1 association, as well as in the TRPC1/IP3RII interaction, which might be of relevance in platelet function. Treatment of human platelets with thapsigargin or thrombin, results in Ca2+-independent association of Homer1 with TRPC1 and IP3RII. In addition, thapsigargin and thrombin enhanced association of Homer1 with STIM1 and Orai1 in a Ca2+-dependent manner. Interference with Homer function by introduction into cells of the synthetic PPKKFR peptide, which emulates the proline-rich sequences of the PPXXF motif, reduced both STIM1/Orai1 and TRPC1/ IP3RII associations, as compared to the introduction of the inactive PPKKRR peptide. The PPKKFR peptide attenuates thrombin-evoked Ca2+ entry and the maintenance of thapsigargin-induced store-operated Ca2+ entry. Finally, the PPKKFR peptide attenuated thrombin-induced platelet aggregation. These findings support an important role for Homer proteins in thrombin-stimulated platelet function, which is likely mediated by the support of agonist-induced Ca2+ entry.
Authors:
Isaac Jardin; Letizia Albarran; Nuria Bermejo; Gines M Salido; Juan A Rosado
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-17
Journal Detail:
Title:  The Biochemical journal     Volume:  -     ISSN:  1470-8728     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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