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Questioning regulation of two-pore channels by NAADP. Messenger (Los Angel) 2013 Jun 01;2(2):113-119 PMID: 24829847 PMCID: PMC4018199

Abstract

NAADP is a potent Ca(2+) mobilizing messenger [1-3]. Since its discovery in 1995 [4] a considerable volume of literature has shown that NAADP couples cell stimulation to endolysosomal Ca(2+) release and thereby the regulation of many cellular functions [5]. However definition of its molecular mechanism of action has proved far from easy. Since 2009, a consensus emerged as several independent groups coalesced upon the two-pore channel (TPC) family as NAADP-activated channels essential for Ca(2+) release from endolysosomal Ca(2+) stores [6-8]. However this view has been recently challenged by data clearly showing that TPCs function as Na(+)-selective channels apparently insensitive to NAADP [9;10]. Given the two fundamental characteristics defining an ion channel comprise the opening stimulus and the nature of the permeant ions, scrutiny of these seeming irreconcilable viewpoints is essential. The purpose of this commentary is to distil the remaining consensus while interrogating these divergent viewpoints. From this analysis, critical experimental needs are identified.

Author List

Marchant JS, Patel S

Author

Jonathan S. Marchant PhD Chair, Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin



View this publication's entry at the Pubmed website PMID: 24829847
jenkins-FCD Prod-130 96200611f8481f0aa4f84230b11dd74d063847a3