MAGI-1a functions as a scaffolding protein for the distal renal tubular basolateral K+ channels

J Biol Chem. 2008 May 2;283(18):12241-7. doi: 10.1074/jbc.M707738200. Epub 2008 Feb 26.

Abstract

As the K(+) recycling pathway for renal Na(+) reabsorption, renal tubular K(+) channels participate in the fluid and electrolyte homeostasis. Previously, we showed that the Kir5.1/Kir4.1 heteromer, which is a heteromeric assembly of two inwardly rectifying K(+) channels, composes the principal basolateral K(+) channels in distal renal tubules and that two motifs in the carboxyl-terminal portion of the Kir4.1 subunit regulate its functional expression. In this study, by using yeast two-hybrid screening, we identified a new isoform of membrane-associated guanylate kinase with inverted domain structure 1 (MAGI-1a-long) as a scaffolding protein for the basolateral K(+) channels. MAGI-1a-long interacted with the PSD-95/Dlg/ZO-1 (PDZ)-binding motif of Kir4.1 by its fifth PDZ domain, and a high salt diet, which could suppress mineralocorticoid secretion, facilitated the interaction. The phosphorylation of serine 377 in the PDZ-binding motif disrupted the interaction, and the disruption of the interaction altered the intracellular localization of the channels from the basolateral side to perinuclear components. These results demonstrate that the phosphorylation-dependent scaffolding of the basolateral K(+) channels by MAGI-1a-long participates in the renal regulation of the fluid and electrolyte homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Cell Line
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Diet
  • Dogs
  • Guanylate Kinases / chemistry
  • Guanylate Kinases / metabolism*
  • Humans
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Kidney Tubules, Distal / cytology
  • Kidney Tubules, Distal / drug effects
  • Kidney Tubules, Distal / metabolism*
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Models, Biological
  • Molecular Sequence Data
  • PDZ Domains
  • Phosphorylation / drug effects
  • Potassium Channels, Inwardly Rectifying / chemistry
  • Potassium Channels, Inwardly Rectifying / metabolism*
  • Protein Binding / drug effects
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism
  • Protein Transport / drug effects
  • Rats
  • Serine / metabolism
  • Sodium Chloride / pharmacology

Substances

  • Kcnj10 (channel)
  • Membrane Proteins
  • Potassium Channels, Inwardly Rectifying
  • Protein Isoforms
  • Sodium Chloride
  • Serine
  • Cyclic AMP-Dependent Protein Kinases
  • Guanylate Kinases
  • Magi1 protein, rat

Associated data

  • GENBANK/AY598951
  • GENBANK/AY598952