CIC voltage-gated anion channels function in organisms ranging from bacteria to animals. CLH-3b is a C. elegans CIC-type channel expressed in the worm oocyte. The biophysical properties of CLH-3b resemble those of mammalian CIC-2. CLH-3b is activated by serine/threonine dephosphorylation during oocyte meiotic maturation and in response to cell swelling. The type 1 phosphatases CeGLC-7alpha/beta and a newly identified Ste20 kinase, GCK-3, regulate CLH-3b. GCK-3 is a homolog of mammalian PASK, which regulates K-CI and Na-K-2CI cotransporters that are involved in epithelial fluid and electrolyte transport, cell volume control and intracellular Cl- homeostasis. gck-3 and clh-3 are co-expressed in the worm oocyte and fluid secreting excretory cell or """"""""kidney"""""""". Knockout of GCK-3 constitutively activates CLH-3b in non-maturing oocytes and causes fertility defects and profound disruption of whole animal fluid balance. My long-term goal is to define the signaling cascades in which GCK-3 functions to regulate CLH-3b and associated salt and water transport processes. Defining these pathways will provide significant and novel insights into CIC regulation and fundamental physiological processes including epithelial Cl- and fluid transport. I will use a combination of molecular biology, forward and reverse genetic analyses, and patch clamp electrophysiology to identify GCK-3 signaling components.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM077904-01
Application #
7112143
Study Section
Special Emphasis Panel (ZRG1-F05-J (20))
Program Officer
Rodewald, Richard D
Project Start
2006-07-01
Project End
2009-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
1
Fiscal Year
2006
Total Cost
$45,976
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212