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

• Type: Article in International Scientific Journal
• Date: 2014

Authors

Goncalves, AP (Author) Other; Cordeiro, JM (Author) Other; Monteiro, J (Author) Other; Munoz, A (Author) Other; Paulo Correia de Sá (Author) ICBAS; Read, ND (Author) Other; Videira, A (Author) Other

Journal

Title: Journal of Cell Science

Vol. 127

Pages: 3817-3829

ISSN: 0021-9533

Publisher: The Company of Biologists Ltd.

Indexing

ISI Web of Knowledge - 5 Citations

Scopus - 5 Citations

Other information

Authenticus ID: P-009-TJ9

DOI: 10.1242/jcs.152058

Abstract (EN): 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 Delta cch-1, Delta fig-1 and Delta yvc-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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13