PIP2 Activates TRPV5 and Releases Its Inhibition by Intracellular Mg2

Jason Lee; Seung-Kuy Cha; Tie-Jun Sun; Chou-Long Huang

doi:10.1085/jgp.200509314

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PIP2 Activates TRPV5 and Releases Its Inhibition by Intracellular Mg2

Journal article

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PIP2 Activates TRPV5 and Releases Its Inhibition by Intracellular Mg2

Jason Lee, Seung-Kuy Cha, Tie-Jun Sun and Chou-Long Huang

The Journal of general physiology, Vol.126(5), pp.439-451

11/01/2005

DOI: 10.1085/jgp.200509314

PMCID: PMC2266600

PMID: 16230466

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Abstract

The transient receptor potential type V5 channel (TRPV5) is a Ca2+-selective TRP channel important for epithelial Ca2+ transport. Intracellular Mg2+ causes a fast voltage-dependent block of the TRPV5 channel by binding to the selectivity filter. Here, we report that intracellular Mg2+ binding to the selectivity filter of TRPV5 also causes a slower reversible conformational change leading to channel closure. We further report that PIP2 activates TRPV5. Activation of TRPV5 by PIP2 is independent of Mg2+. Yet, PIP2 decreases sensitivity of the channel to the Mg2+-induced slow inhibition. Mutation of aspartate-542, a critical Mg2+-binding site in the selectivity filter, abolishes Mg2+-induced slow inhibition. PIP2 has no effects on Mg2+-induced voltage-dependent block. Thus, PIP2 prevents the Mg2+-induced conformational change without affecting Mg2+ binding to the selectivity filter. Hydrolysis of PIP2 via receptor activation of phospholipase C sensitizes TRPV5 to the Mg2+-induced slow inhibition. These results provide a novel mechanism for regulation of TRP channels by phospholipase C–activating hormones via alteration of the sensitivity to intracellular Mg2+.

Details

Title: Subtitle: PIP2 Activates TRPV5 and Releases Its Inhibition by Intracellular Mg2
Creators: Jason Lee - The University of Texas Southwestern Medical Center
Seung-Kuy Cha - The University of Texas Southwestern Medical Center
Tie-Jun Sun - The University of Texas Southwestern Medical Center
Chou-Long Huang - The University of Texas Southwestern Medical Center
Resource Type: Journal article
Publication Details: The Journal of general physiology, Vol.126(5), pp.439-451
DOI: 10.1085/jgp.200509314
PMID: 16230466
PMCID: PMC2266600
NLM abbreviation: J Gen Physiol
ISSN: 0022-1295
eISSN: 1540-7748
Language: English
Date published: 11/01/2005
Academic Unit: Nephrology; Internal Medicine
Record Identifier: 9984360041602771

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