Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-1411
Hu, M C; Fan, L; Crowder, L A; Karim-Jimenez, Z; Murer, H; Moe, O W (2001). Dopamine acutely stimulates Na+/H+ exchanger (NHE3) endocytosis via clathrin-coated vesicles: dependence on protein kinase A-mediated NHE3 phosphorylation. Journal of Biological Chemistry, 276(29):26906-26915.
Dopamine (DA) is a key hormone in mammalian sodium homeostasis. DA induces natriuresis via acute inhibition of the renal proximal tubule apical membrane Na(+)/H(+) exchanger NHE3. We examined the mechanism by which DA inhibits NHE3 in a renal cell line. DA acutely decreases surface NHE3 antigen in dose- and time-dependent fashion without altering total cellular NHE3. Although DA(1) receptor agonist alone decreases surface NHE3, simultaneous DA(2) agonist synergistically enhances the effect of DA(1). Decreased surface NHE3 antigen, caused by stimulation of NHE3 endocytosis, is dependent on intact functioning of the GTPase dynamin and involves increased binding of NHE3 to the adaptor protein AP2. DA-stimulated NHE3 endocytosis can be blocked by pharmacologic or genetic protein kinase A inhibition or by mutation of two protein kinase A target serines (Ser-560 and Ser-613) on NHE3. We conclude that one mechanism by which DA induces natriuresis is via protein kinase A-mediated phosphorylation of proximal tubule NHE3 leading to endocytosis of NHE3 via clathrin-coated vesicles.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Institute of Physiology|
07 Faculty of Science > Institute of Physiology
|DDC:||570 Life sciences; biology|
|Date:||20 July 2001|
|Deposited On:||11 Feb 2008 13:23|
|Last Modified:||23 Nov 2012 13:29|
|Publisher:||American Society for Biochemistry and Molecular Biology|
|Additional Information:||This research was originally published in Hu, M C; Fan, L; Crowder, L A; Karim-Jimenez, Z; Murer, H; Moe, O W. Dopamine acutely stimulates Na+/H+ exchanger (NHE3) endocytosis via clathrin-coated vesicles: dependence on protein kinase A-mediated NHE3 phosphorylation. J. Biol. Chem. 2001, 276(29):26906-15. © the American Society for Biochemistry and Molecular Biology.|
|WoS Citation Count:||83|
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