Cch1 restores intracellular Ca2+ in fungal cells during endoplasmic reticulum stress.

The Journal of Biological Chemistry
Min-Pyo HongAngie Gelli

Abstract

Pathogens endure and proliferate during infection by exquisitely coping with the many stresses imposed by the host to prevent pathogen survival. Recent evidence has shown that fungal pathogens and yeast respond to insults to the endoplasmic reticulum (ER) by initiating Ca(2+) influx across their plasma membrane. Although the high affinity Ca(2+) channel, Cch1, and its subunit Mid1, have been suggested as the protein complex responsible for mediating Ca(2+) influx, a direct demonstration of the gating mechanism of the Cch1 channel remains elusive. In this first mechanistic study of Cch1 channel activity we show that the Cch1 channel from the model human fungal pathogen, Cryptococcus neoformans, is directly activated by the depletion of intracellular Ca(2+) stores. Electrophysiological analysis revealed that agents that enable ER Ca(2+) store depletion promote the development of whole cell inward Ca(2+) currents through Cch1 that are effectively blocked by La(3+) and dependent on the presence of Mid1. Cch1 is permeable to both Ca(2+) and Ba(2+); however, unexpectedly, in contrast to Ca(2+) currents, Ba(2+) currents are steeply voltage-dependent. Cch1 maintains a strong Ca(2+) selectivity even in the presence of high concentration...Continue Reading

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Citations

Jan 22, 2011·The Journal of Biological Chemistry·D Christian MartinKyle W Cunningham
Jul 24, 2012·Molecular Biology and Evolution·Benjamin J LiebeskindHarold H Zakon
Jan 30, 2013·PloS One·Brett S KirbyScott Earley
Mar 7, 2013·Genetics·Martha S Cyert, Caroline C Philpott
Aug 2, 2014·PloS One·Patrícia Alves de CastroGustavo H Goldman
Dec 10, 2016·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Toshihiko ChoHidetoshi Iida
Oct 27, 2016·Scientific Reports·Kristelle Desfossés-BaronHugo Wurtele
Jun 6, 2013·The Journal of Biological Chemistry·Charulatha GururajAmy Chang
May 5, 2017·Frontiers in Microbiology·Fang-Yu HwuRuey-Fen Liou
Jul 20, 2014·Journal of Cell Science·A Pedro GonçalvesArnaldo Videira
May 1, 2021·Biomolecules·Marina VolkovaAlbert Guskov

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