QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 18, Issue 11, 4508-4518, November 2007

This Article Full Text Full Text (PDF) All Versions of this Article: E06-08-0711v1 18/11/4508    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kimura, T. Articles by Caplan, M. J. Search for Related Content PubMed PubMed Citation Articles by Kimura, T. Articles by Caplan, M. J.

Arrestins and Spinophilin Competitively Regulate Na⁺,K⁺-ATPase Trafficking through Association with a Large Cytoplasmic Loop of the Na⁺,K⁺-ATPase

Tohru Kimura^*, Patrick B. Allen, Angus C. Nairn, and Michael J. Caplan^*

Departments of *Cellular and Molecular Physiology and Psychiatry, Yale University School of Medicine, New Haven, CT 06520-8026

Submitted August 15, 2006; Revised July 31, 2007; Accepted August 28, 2007
Monitoring Editor: J. Silvio Gutkind

The activity and trafficking of the Na⁺,K⁺-ATPase are regulated by several hormones, including dopamine, vasopressin, and adrenergic hormones through the action of G-protein–coupled receptors (GPCRs). Arrestins, GPCR kinases (GRKs), 14-3-3 proteins, and spinophilin interact with GPCRs and modulate the duration and magnitude of receptor signaling. We have found that arrestin 2 and 3, GRK 2 and 3, 14-3-3 , and spinophilin directly associate with the Na⁺,K⁺-ATPase and that the associations with arrestins, GRKs, or 14-3-3 are blocked in the presence of spinophilin. In COS cells that overexpressed arrestin, the Na⁺,K⁺-ATPase was redistributed to intracellular compartments. This effect was not seen in mock-transfected cells or in cells expressing spinophilin. Furthermore, expression of spinophilin appeared to slow, whereas overexpression of -arrestins accelerated internalization of the Na⁺,K⁺-ATPase endocytosis. We also find that GRKs phosphorylate the Na⁺,K⁺-ATPase in vitro on its large cytoplasmic loop. Taken together, it appears that association with arrestins, GRKs, 14-3-3 , and spinophilin may be important modulators of Na⁺,K⁺-ATPase trafficking.

Address correspondence to: Michael Caplan (michael.caplan{at}yale.edu).

Abbreviations used: PKA, protein kinase A; PKC, protein kinase C; HA, hemagglutinin; GPCR, G-protein–coupled receptor; GRK, G-protein–coupled receptor kinase.

This article has been cited by other articles:

				J. Tian and Z.-j. Xie The Na-K-ATPase and Calcium-Signaling Microdomains Physiology, August 1, 2008; 23(4): 205 - 211. [Abstract] [Full Text] [PDF]