title: The potassium channel Kir4.1 associates with the dystrophin-glycoprotein complex via alpha-syntrophin in glia.
abstract: One of the major physiological roles of potassium channels in glial cells is to promote "potassium spatial buffering" in the central nervous system, a process necessary to maintain an optimal potassium concentration in the extracellular environment. This process requires the precise distribution of potassium channels accumulated at high density in discrete subdomains of glial cell membranes. To obtain a better understanding of how glial cells selectively target potassium channels to discrete membrane subdomains, we addressed the question of whether the glial inwardly rectifying potassium channel Kir4.1 associates with the dystrophin-glycoprotein complex (DGC). Immunoprecipitation experiments revealed that Kir4.1 is associated with the DGC in mouse brain and cultured cortical astrocytes. In vitro immunoprecipitation and pull-down assays demonstrated that Kir4.1 can bind directly to alpha-syntrophin, requiring the presence of the last three amino acids of the channel (SNV), a consensus PDZ domain-binding motif. Furthermore, Kir4.1 failed to associate with the DGC in brains from alpha-syntrophin knockout mice. These results suggest that Kir4.1 is localized in glial cells by its association with the DGC through a PDZ domain-mediated interaction with alpha-syntrophin and suggest an important role for the DGC in central nervous system physiology.
authors.affiliation: Department of Neuroscience, University of Minnesota, 321 Church Street SE, Minneapolis, MN 55455, USA.
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Connors
authors.forename: Marvin E
authors.initials: ME
authors.lastname: Adams
authors.forename: Stanley C
authors.initials: SC
authors.lastname: Froehner
authors.forename: Paulo
authors.initials: P
authors.lastname: Kofuji
mesh_terms: D000818:Animals; D051401:Aquaporin 4; D020346:Aquaporins / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D002135:Calcium-Binding Proteins; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000494:pharmacology; D016189:Dystrophin / Q000737:chemistry*; D005982:Glutathione Transferase / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009124:Muscle Proteins / Q000737:chemistry* / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism*; D015221:Potassium Channels / Q000737:chemistry; D024661:Potassium Channels, Inwardly Rectifying / Q000737:chemistry / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D020346:Aquaporins; D002135:Calcium-Binding Proteins; D003432:Cross-Linking Reagents; D016189:Dystrophin; D006023:Glycoproteins; D008565:Membrane Proteins; D009124:Muscle Proteins; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; C091825:syntrophin alpha1; D005982:Glutathione Transferase