CGC Bibliography Paper 5398

Cell cycle- and swelling-induced activation of a Caenorhabditis elegans CIC channel is mediated by CeGLC-7alpha/beta phosphatases.

Rutledge E, Denton J, Strange K

Medline:

12163466

Citation:

Journal of Cell Biology 158: 435-444 2002

Type:

ARTICLE

Genes:

clh-3 clh-5 glc-7

Abstract:

CIC voltage-gated anion channels have been identified in bacteria, yeast, plants, and animals. The biophysical and structural properties of CICs have been studied extensively, but relatively little is known about their precise physiological functions. Furthermore, virtually nothing is known about the signaling pathways and molecular mechanisms that regulate channel activity. The nematode Caenorhabditis elegans provides significant experimental advantages for characterizing ion channel function and regulation. We have shown previously that the CIC Cl- channel homologue CLH-3 is expressed in C. elegans oocytes, and that it is activated during meiotic maturation and by cell swelling. We demonstrate here that depletion of intracellular ATP or removal of Mg2+, experimental maneuvers that inhibit kinase function, constitutively activate CLH-3. Maturation- and swelling-induced channel activation are inhibited by type 1 serine/threonine phosphatase inhibitors. RNA interference studies demonstrated that the type 1 protein phosphatases CeGLC-7alpha and beta, both of which play essential regulatory roles in mitotic and meiotic cell cycle events, mediate CLH-3 activation. We have suggested previously that CLH-3 and mammalian CIC-2 are orthologues that play important roles in heterologous cell-cell interactions, intercellular communication, and regulation of cell cycle-dependent physiological processes. Consistent with this hypothesis, we show that heterologously expressed rat CIC-2 is also activated by serine/threonine dephosphorylation, suggesting that the two channels have