Activation of a TRP-like channel and intracellular Ca2+ dynamics during phospholipase-C-mediated cell death

A. Pedro Gonçalves, J. Miguel Cordeiro, João Monteiro, Alberto Muñoz, Paulo Correia-de-Sá, Nick D. Read, Arnaldo Videira

研究成果: Article同行評審

15 引文 斯高帕斯(Scopus)

摘要

The model organism Neurospora crassa undergoes programmed cell death when exposed to staurosporine. Here, we show that staurosporine causes defined changes in cytosolic free Ca2+ ([Ca2+]c) dynamics and a distinct Ca2+ signature that involves Ca2+ influx from the external medium and internal Ca2+ stores. We investigated the molecular basis of this Ca2+ response by using [Ca2+]c measurements combined with pharmacological and genetic approaches. Phospholipase C was identified as a pivotal player during cell death, because modulation of the phospholipase C signaling pathway and deletion of PLC-2, which we show to be involved in hyphal development, results in an inability to trigger the characteristic staurosporine-induced Ca2+ signature. Using Δcch-1, Δfig-1 and Δyvc-1 mutants and a range of inhibitors, we show that extracellular Ca2+ entry does not occur through the hitherto described high- and low-affinity Ca2+ uptake systems, but through the opening of plasma membrane channels with properties resembling the transient receptor potential (TRP) family. Partial blockage of the response to staurosporine after inhibition of a putative inositol-1,4,5-trisphosphate (IP3) receptor suggests that Ca2+ release from internal stores following IP3 formation combines with the extracellular Ca2+ influx.

原文English
頁(從 - 到)3817-3829
頁數13
期刊Journal of Cell Science
127
發行號17
DOIs
出版狀態Published - 2014

All Science Journal Classification (ASJC) codes

  • 細胞生物學

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