Abstract：
:Changes of intracellular and extracellular pH are involved in a variety of physiological and pathological processes, in which regulation of the Ca(2+) release activated Ca(2+) channel (I CRAC) by pH has been implicated. Ca(2+) entry mediated by I CRAC has been shown to be regulated by acidic or alkaline pH. Whereas several amino acid residues have been shown to contribute to extracellular pH (pHo) sensitivity, the molecular mechanism for intracellular pH (pHi) sensitivity of Orai1/STIM1 is not fully understood. By investigating a series of mutations, we find that the previously identified residue E106 is responsible for pHo sensitivity when Ca(2+) is the charge carrier. Unexpectedly, we identify that the residue E190 is responsible for pHo sensitivity when Na(+) is the charge carrier. Furthermore, the intracellular mutant H155F markedly diminishes the response to acidic and alkaline pHi, suggesting that H155 is responsible for pHi sensitivity of Orai1/STIM1. Our results indicate that, whereas H155 is the intracellular pH sensor of Orai1/STIM1, the molecular mechanism of external pH sensitivity varies depending on the permeant cations. As changes of pH are involved in various physiological/pathological functions, Orai/STIM channels may be an important mediator for various physiological and pathological processes associated with acidosis and alkalinization.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Tsujikawa H,Yu AS,Xie J,Yue Z,Yang W,He Y,Yue Ldoi
10.1038/srep16747subject
Has Abstractpub_date
2015-11-18 00:00:00pages
16747issn
2045-2322pii
srep16747journal_volume
5pub_type
杂志文章abstract：:Liver resection remains the popular treatment for hepatocellular carcinoma (HCC). The aim of this study was to explore the alteration of immune cells in HCC patients with liver resections. Nineteen patients were included and their peripheral blood samples were taken before and after liver resections for immune-cell an...
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