The ability to sense and respond to changes in cell volume is a universal property of all cells. Changes in cell volume play important signaling roles in controlling cell growth and proliferation. Cell volume regulation is an essential """"""""housekeeping"""""""" function. Despite their physiological importance, little is known about the molecular nature of volume- sensitive channels, or about how cell size is sensed and regulates channel gating. C. elegans offers significant experimental advantages for defining the function and regulation of ion channels. However, because of the relative inaccessibility of somatic cells in adult nematodes, direct electrophysiological studies of ion channel activity are extremely difficult. To circumvent this problem, I developed techniques to patch clamp C. elegans oocytes. My studies have identified a swelling- activated Inwardly Rectifying Cl-Channel termed IRCC. IRCC activity changes dramatically during oocyte development suggesting that the channel may play an important role in regulating oocyte growth and/or the cell cycle. Preliminary RNA interference data suggest that IRCC is encoded by a ClC channel gene. The central goal of my proposal is to combine electrophysiological measurements with genomic analysis and molecular biology methods to identify the gene(s) encoding IRCC and to begin characterizing channel regulation. Identification of the channel genes will ultimately enable them to be manipulated at the molecular level. This in turn will provide insight into the role of IRCC in oogenesis and into the mechanisms by which it senses and is regulated by cell size.
| Rutledge, Eric; Denton, Jerod; Strange, Kevin (2002) Cell cycle- and swelling-induced activation of a Caenorhabditis elegans ClC channel is mediated by CeGLC-7alpha/beta phosphatases. J Cell Biol 158:435-44 |
