Two channels, one program

Abstract

The biophysical and structural characteristics of chloride ion channels have been studied extensively, but little is known about the molecular regulation and signaling pathways associated with these highly conserved proteins. Rutledge et al. (page 435) analyzed the activation of the CLH-3 chloride ion channel in C. elegans during meioitic cell cycle progression and in response to oocyte swelling. The work demonstrates the utility of the worm system in studying these channels, and suggests that CLH-3 and its putative mammalian orthologue, ClC-2, respond to similar regulatory inputs to carry out similar physiological functions. Figure A phosphatase inhibitor (CA) prevents meiotic maturation–induced current. The authors found that during oocyte maturation, or in response to oocyte swelling, CLH-3 is activated by serine/threonine dephosphorylation. RNAi inhibition demonstrates that the dephosphorylation is mediated by CeGLC-7α and CeGLC-7β, phosphatases that help to regulate meiotic and mitotic cell cycles in worms. Rat ClC-2 heterologously expressed in mammalian cells is also activated by serine/threonine dephosphorylation, suggesting that the two channels share a common regulatory mechanism, despite their wide evolutionary separation. Rutledge et al. suggest that both channels may depolarize membranes to transduce signals between cell types, such as worm oocytes and the surrounding contractile sheath cells, that are coupled by gap junctions. ▪