Intracellular Chloride Channels: Determinants of Function in the Endosomal Pathway

Science's STKE  18 May 2004:
Vol. 2004, Issue 233, pp. re8
DOI: 10.1126/stke.2332004re8

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Endosomes, and related subcellular compartments, contain various Cl channels in the ClC family. In this review, we describe the known roles of intracellular Cl channels and also explore some of the functional implications of transmembrane Cl flux in these organelles. Cl influx acts to control intralumenal pH, both by shunting the effects of the proton pump on membrane potential and, possibly, through direct effects of Cl on the proton pump. Changes in intralumenal pH likely help regulate membrane trafficking. We propose that changes in intralumenal Cl concentration ([Cl]) could theoretically play a direct role in regulating membrane trafficking and organellar function through effects on chloride-sensitive proteins in the vesicular membrane, which could transduce information about intralumenal [Cl] to the outside of the vesicle and thereby recruit various signaling molecules. We present a model in which regulation of cytosolic [Cl] and vesicular Cl conductance could help control the amount or type of neurotransmitter stored in a particular population of synaptic vesicles.

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