Regulation of the rat brain Na+ -driven Cl-/HCO3 - exchanger involves protein kinase A and a multiprotein signaling complex.
The Na(+)-driven Cl(-)/HCO(3)(-) exchanger (NCBE) plays an important role in the regulation of intracellular pH (pH(i)). We previously identified two variants of NCBE from rat brain of which the variant with a carboxyterminal PSD-95/Dlg/ZO-1 (PDZ) motif (rb2NCBE) colocalized with the actin cytoskeleton. Increased rb2NCBE activity by PKA inhibition and reduction by forskolin and cAMP agonist suggest PKA regulation of NCBE. Disruption of actin filaments also decreased rb2NCBE activity. EBP50 and FLAG-rb2NCBE were reciprocally co-immunoprecipitated from rb2NCBE transfected cells. It is concluded that NCBE activity is inhibited by PKA and depends on the integrity of the actin cytoskeleton within a multiprotein complex at the plasma membrane.
Lee
Yong-Sun
YS
Department of Anesthesia, S272 Stanford University School of Medicine, Stanford, CA 94305-5117, USA.
Ouyang
Yi-Bing
YB
Giffard
Rona G
RG
D000199:Actins / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D027963:Chloride-Bicarbonate Antiporters / Q000235:genetics / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003571:Cytochalasin B / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004789:Enzyme Activation; D006863:Hydrogen-Ion Concentration; D051379:Mice; D046912:Multiprotein Complexes; D041681:NIH 3T3 Cells; D010750:Phosphoproteins / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers; D000099149:Ezrin
D000199:Actins; D000262:Adenylyl Cyclases; D002352:Carrier Proteins; D027963:Chloride-Bicarbonate Antiporters; D017868:Cyclic AMP-Dependent Protein Kinases; D003571:Cytochalasin B; D003598:Cytoskeletal Proteins; D046912:Multiprotein Complexes; D010750:Phosphoproteins; D020033:Protein Isoforms; D012964:Sodium; D017923:Sodium-Hydrogen Exchangers; D000099149:Ezrin; C093376:sodium-hydrogen exchanger regulatory factor