Distinct structural domains of caveolin-1 independently regulate Ca2+ release-activated Ca2+ channels and Ca2+ microdomain-dependent gene expression

Yi Chun Yeh, Anant B. Parekh

研究成果: Article同行評審

27 引文 斯高帕斯(Scopus)


In eukaryotic cells, calcium entry across the cell surface activates nuclear gene expression, a process critically important for cell growth and differentiation, learning, and memory and immune cell functions. In immune cells, calcium entry occurs through store-operated Ca2+ release-activated Ca2+ (CRAC) channels, comprised of STIM1 and Orai1 proteins. Local calcium entry through CRAC channels activates expression of c-fos- and nuclear factor of activated T cells (NFAT)-dependent genes. Although c-fos and NFAT often interact to activate gene expression synergistically, they can be activated independently of one another to regulate distinct genes. This raises the question of how one transcription factor can be activated and not the other when both are stimulated by the same trigger. Here, we show that the lipid raft scaffolding protein caveolin-1 interacts with the STIM1-Orai1 complex to increase channel activity. Phosphorylation of tyrosine 14 on caveolin-1 regulates CRAC channel-evoked c-fos activation without impacting the NFAT pathway or Orai1 activity. Our results reveal that structurally distinct domains of caveolin-1 selectively regulate the ability of local calcium to activate distinct transcription factors. More generally, our findings reveal that modular regulation by a scaffolding protein provides a simple, yet effective, mechanism to tunnel a local signal down a specific pathway.

頁(從 - 到)1341-1349
期刊Molecular and Cellular Biology
出版狀態Published - 2015

All Science Journal Classification (ASJC) codes

  • 分子生物學
  • 細胞生物學


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