Laminin-induced aggregation of the inwardly rectifying potassium channel, Kir4.1, and the water-permeable channel, AQP4, via a dystroglycan-containing complex in astrocytes.
Dystroglycan (DG) is part of a multiprotein complex that links the extracellular matrix to the actin cytoskeleton of muscle fibers and that is involved in aggregating acetylcholine receptors at the neuromuscular junction. This complex is also expressed in regions of the central nervous system where it is localized to both neuronal and glial cells. DG and the inwardly rectifying potassium channels, Kir4.1, are concentrated at the interface of astroglia and small blood vessels. These channels are involved in siphoning potassium released into the extracellular space after neuronal excitation. This raises the possibility that DG may be involved in targeting Kir4.1 channels to specific domains of astroglia. To address this question, we used mixed hippocampal cultures to investigate the distribution of DG, syntrophin, dystrobrevin, and Kir4.1 channels, as well as aquaporin-permeable water channels, AQP4. These proteins exhibit a similar distribution pattern and form aggregates in astrocytes cultured on laminin. Both DG and syntrophin colocalize with Kir4.1 channel aggregates in astrocytes. Similarly, DG colocalizes with AQP4 channel aggregates. Quantitative studies show a significant increase of Kir4.1 and AQP4 channel aggregates in astrocytes cultured in the presence of laminin when compared with those in the absence of laminin. These findings show that laminin has a role in Kir4.1 and AQP4 channel aggregation and suggest that this may be mediated via a dystroglycan-containing complex. This study reveals a novel functional role for DG in brain including K+ buffering and water homeostasis.
Guadagno
Eric
E
Département de Sciences Biologiques, Université de Montréal, Montréal, Québec, Canada.
Moukhles
Hakima
H
D000818:Animals; D000831:Animals, Newborn; D051401:Aquaporin 4; D020346:Aquaporins / Q000187:drug effects / Q000378:metabolism*; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D049030:Dystroglycans; D049029:Dystrophin-Associated Proteins; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D007797:Laminin / Q000378:metabolism* / Q000494:pharmacology; D046911:Macromolecular Substances; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D046912:Multiprotein Complexes; D009124:Muscle Proteins / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011940:Receptor Aggregation / Q000187:drug effects / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology
C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D020346:Aquaporins; D003598:Cytoskeletal Proteins; D049029:Dystrophin-Associated Proteins; D007797:Laminin; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D009124:Muscle Proteins; D009479:Neuropeptides; D024661:Potassium Channels, Inwardly Rectifying; C091824:syntrophin; D049030:Dystroglycans; D011188:Potassium