Distinct detergent-resistant membrane microdomains (lipid rafts) respectively harvest K(+) and water transport systems in brain astroglia.
The detergent-resistant microdomains (DRM) of cell membranes scaffold different molecules and regulate cell functions by orchestrating various signaling pathways including G-proteins and tyrosine kinase. Here we report a novel role for DRM in astroglial cells. K(+)-buffering inwardly rectifying Kir4.1 channels and the water channel AQP4 are expressed in astrocytes and they may be functionally coupled to maintain ionic and osmotic homeostasis in the brain. Kir4.1 and AQP4 channel proteins were abundant in noncaveloar DRM in the brain and also in HEK293T cells when exogenously expressed. In HEK293T cells, depletion of membrane cholesterol by methyl-beta-cyclodextrin (MbetaCD) resulted in loss of Kir4.1 association with DRM and its channel activity but did not affect either the distribution or the function of AQP4. Immunolabeling showed that Kir4.1 and AQP4 were occasionally distributed in close proximity but in distinct compartments of the astroglial cell membrane. Astroglial noncaveolar DRM may therefore be made up of at least two distinct compartments, MbetaCD-sensitive and MbetaCD-resistant microdomains, which control localization and function of, respectively, Kir and AQP4 channels on the cell membrane.
Hibino
Hiroshi
H
Division of Molecular and Cellular Pharmacology, Department of Pharmacology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
Kurachi
Yoshihisa
Y
D000818:Animals; D051401:Aquaporin 4 / Q000187:drug effects / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism* / Q000648:ultrastructure; D001834:Body Water / Q000502:physiology; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D002451:Cell Compartmentation / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011188:Potassium / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology; D047392:beta-Cyclodextrins / Q000494:pharmacology; D000098854:Kcnj10 Channel
C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D000098854:Kcnj10 Channel; D024661:Potassium Channels, Inwardly Rectifying; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D002784:Cholesterol; D011188:Potassium