PI(3,5)P(2) Controls Membrane Trafficking by Direct Activation of Mucolipin Ca(2+) Release Channels in the Endolysosome

Overview

Journal Nat Commun

Specialty Biology

Date 2010 Aug 31

PMID 20802798

Citations 346

Authors

Xian-Ping Dong

Dongbiao Shen

Xiang Wang

Taylor Dawson

Xinran Li

Qi Zhang

Xiping Cheng

Yanling Zhang

Lois S Weisman

Markus Delling

Haoxing Xu

Affiliations

Soon will be listed here.

Abstract

Membrane fusion and fission events in intracellular trafficking are controlled by both intraluminal Ca(2+) release and phosphoinositide (PIP) signalling. However, the molecular identities of the Ca(2+) release channels and the target proteins of PIPs are elusive. In this paper, by direct patch-clamping of the endolysosomal membrane, we report that PI(3,5)P(2), an endolysosome-specific PIP, binds and activates endolysosome-localized mucolipin transient receptor potential (TRPML) channels with specificity and potency. Both PI(3,5)P(2)-deficient cells and cells that lack TRPML1 exhibited enlarged endolysosomes/vacuoles and trafficking defects in the late endocytic pathway. We find that the enlarged vacuole phenotype observed in PI(3,5)P(2)-deficient mouse fibroblasts is suppressed by overexpression of TRPML1. Notably, this PI(3,5)P(2)-dependent regulation of TRPML1 is evolutionarily conserved. In budding yeast, hyperosmotic stress induces Ca(2+) release from the vacuole. In this study, we show that this release requires both PI(3,5)P(2) production and a yeast functional TRPML homologue. We propose that TRPMLs regulate membrane trafficking by transducing information regarding PI(3,5)P(2) levels into changes in juxtaorganellar Ca(2+), thereby triggering membrane fusion/fission events.

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