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PMID: 17804821 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Arrestins and spinophilin competitively regulate Na+,K+-ATPase trafficking through association with a large cytoplasmic loop of the Na+,K+-ATPase.

Molecular biology of the cell ·Vol. 18 ·No. 11 ·2007-11-00 ·Pages 4508-18

Kimura T, Allen PB, Nairn AC, Caplan MJ

Abstract

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 epsilon, and spinophilin directly associate with the Na(+),K(+)-ATPase and that the associations with arrestins, GRKs, or 14-3-3 epsilon 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 beta-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 epsilon, and spinophilin may be important modulators of Na(+),K(+)-ATPase trafficking.

MeSH Terms
14-3-3 Proteins/metabolism Animals Arrestin/metabolism Binding, Competitive Cell Line Chlorocebus aethiops Choroid Plexus/metabolism Cytoplasm/metabolism G-Protein-Coupled Receptor Kinases/metabolism Kidney/metabolism Mice Microfilament Proteins/metabolism Nerve Tissue Proteins/metabolism Phosphorylation Protein Binding Protein Subunits/genetics,metabolism Protein Transport Rabbits Sodium-Potassium-Exchanging ATPase/genetics,metabolism
Chemicals
14-3-3 Proteins Arrestin Microfilament Proteins Nerve Tissue Proteins Protein Subunits neurabin G-Protein-Coupled Receptor Kinases Sodium-Potassium-Exchanging ATPase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kimura Tohru
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520-8026, USA.
Allen Patrick B
Nairn Angus C
Caplan Michael J
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e06-08-0711
Published
2007-11-00
Epub
2007-00-05
Pages
4508-18
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC2043564
Subset
IM
Grants
NIMH NIH HHS · P01 MH040899 · United States
NIDDK NIH HHS · R56 DK072614 · United States
NIMH NIH HHS · P50 MH074866 · United States
NIMH NIH HHS · MH40899 · United States
NIDDK NIH HHS · DK072614 · United States
NIDDK NIH HHS · DK17433 · United States
NIMH NIH HHS · MH074866 · United States
NIDDK NIH HHS · P01 DK017433 · United States
NIDDK NIH HHS · R01 DK072614 · United States
External Links
PubMed source DOI: 10.1091/mbc.e06-08-0711 PMC Full Text View journal details
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