MAGI-1a functions as a scaffolding protein for the distal renal tubular basolateral K+ channels.
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.
Tanemoto
Masayuki
M
Division of Nephrology, Hypertension, and Endocrinology, Department of Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-857, Japan. mtanemoto-tky@umin.ac.jp
Toyohara
Takafumi
T
Abe
Takaaki
T
Ito
Sadayoshi
S
D020816:Amino Acid Motifs; D000818:Animals; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004032:Diet; D004285:Dogs; D051528:Guanylate Kinases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007686:Kidney Tubules, Distal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D054731:PDZ Domains; D010766:Phosphorylation / Q000187:drug effects; D024661:Potassium Channels, Inwardly Rectifying / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D012694:Serine / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology; D000098854:Kcnj10 Channel
D000098854:Kcnj10 Channel; D008565:Membrane Proteins; D024661:Potassium Channels, Inwardly Rectifying; D020033:Protein Isoforms; D012965:Sodium Chloride; D012694:Serine; D017868:Cyclic AMP-Dependent Protein Kinases; D051528:Guanylate Kinases; C508141:Magi1 protein, rat