title: Evidence that pericytes regulate aquaporin-4 polarization in mouse cortical astrocytes.
abstract: Aquaporin-4 (AQP4) water channels are concentrated in astrocytic endfoot membranes at the brain-blood and brain-cerebrospinal fluid interfaces. The mechanisms underpinning the polarized distribution of AQP4 are poorly understood. Here we tested the hypothesis that pericytes regulate AQP4 anchoring to perivascular astrocytic endfoot membranes. AQP4 immunofluorescence of brain sections obtained from novel transgenic double reporter mice expressing enhanced green fluorescent protein (eGFP) in astrocytes and Discoma Red (DsRed) in pericytes revealed strong AQP4 signal in astrocytic processes adjacent to pericytes. Quantitative immunogold analysis of C57BL/6 mice showed that the AQP4 expression was higher in endfoot membranes abutting pericytes than in those facing endothelial cells. Similar findings were made for α-syntrophin, a member of the dystrophin-associated protein complex (DAPC). The enrichment of α-syntrophin in membranes ensheathing pericytes persisted after Aqp4 gene deletion. Our data support the concept that pericytes regulate AQP4 polarization.
authors: Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, P.O. Box 1137, Blindern, 0318, Oslo, Norway.
authors: Georg Andreas
authors: GA
authors: Gundersen
authors: Gry Fluge
authors: GF
authors: Vindedal
authors: Oivind
authors: O
authors: Skare
authors: Erlend A
authors: EA
authors: Nagelhus
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000032:analysis*; D001253:Astrocytes / Q000378:metabolism* / Q000648:ultrastructure*; D002135:Calcium-Binding Proteins / Q000032:analysis; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D016764:Cell Polarity; D002540:Cerebral Cortex / Q000648:ultrastructure*; D005455:Fluorescent Antibody Technique; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000032:analysis; D020286:Pericytes / Q000648:ultrastructure*
chemical_list: C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D002135:Calcium-Binding Proteins; D008565:Membrane Proteins; D009124:Muscle Proteins; C091825:syntrophin alpha1
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