Shank2 associates with and regulates Na+/H+ exchanger 3.
Na+/H+ exchanger 3 (NHE3) plays a pivotal role in transepithelial Na+ and HCO3(-) absorption across a wide range of epithelia in the digestive and renal-genitourinary systems. Accumulating evidence suggests that PDZ-based adaptor proteins play an important role in regulating the trafficking and activity of NHE3. A search for NHE3-binding modular proteins using yeast two-hybrid assays led us to the PDZ-based adaptor Shank2. The interaction between Shank2 and NHE3 was further confirmed by immunoprecipitation and surface plasmon resonance studies. When expressed in PS120/NHE3 cells, Shank2 increased the membrane expression and basal activity of NHE3 and attenuated the cAMP-dependent inhibition of NHE3 activity. Furthermore, knock-down of native Shank2 expression in Caco-2 epithelial cells by RNA interference decreased NHE3 protein expression as well as activity but amplified the inhibitory effect of cAMP on NHE3. These results indicate that Shank2 is a novel NHE3 interacting protein that is involved in the fine regulation of transepithelial salt and water transport through affecting NHE3 expression and activity.
Han
WonSun
W
Department of Pharmacology, Brain Korea 21 Project for Medical Science, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 120-752, Korea.
Kim
Kyung Hwan
KH
Jo
Min Jae
MJ
Lee
Ji Hyun
JH
Yang
Jinhee
J
Doctor
R Brian
RB
Moe
Orson W
OW
Lee
Jinu
J
Kim
Eunjoon
E
Lee
Min Goo
MG
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms; D006224:Cricetinae; D017353:Gene Deletion; D017930:Genes, Reporter; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D014162:Transfection
D009419:Nerve Tissue Proteins; C122162:SHANK2 protein, human; D017923:Sodium-Hydrogen Exchangers