期刊
JOURNAL OF COMPARATIVE NEUROLOGY
卷 528, 期 3, 页码 407-418出版社
WILEY
DOI: 10.1002/cne.24763
关键词
astrocytes; basement membrane; blood-brain barrier; >; >; >; >; RRID; RGD_1566457; water permeability
资金
- Canadian Institutes of Health Research [20R47867]
The basement membrane that seperates the endothelial cells and astrocytic endfeet that comprise the blood-brain barrier is rich in collagen, laminin, agrin, and perlecan. Previous studies have demonstrated that the proper recruitment of the water-permeable channel aquaporin-4 (AQP4) to astrocytic endfeet is dependent on interactions between laminin and the receptor dystroglycan. In this study, we conducted a deeper investigation into how the basement membrane might further regulate the expression, localization, and function of AQP4, using primary astrocytes as a model system. We found that treating these cells with laminin causes endogenous agrin to localize to the cell surface, where it co-clusters with beta-dystroglycan (beta-DG). Conversely, agrin sliencing profoundly disrupts beta-DG clustering. As in the case of laminin111, Matrigel (TM), a complete basement membrane analog, also causes the clustering of AQP4 and beta-DG. This clustering, whether induced by laminin111 or Matrigel (TM) is inhibited when the astrocytes are first incubated with an antibody against the gamma 1 subunit of laminin, suggesting that the latter is crucial to the process. Finally, we showed that laminin111 appears to negatively regulate AQP4-mediated water transport in astrocytes, suppressing the cell swelling that occurs following a hypoosmotic challenge. This suppression is abolished if DG expression is silenced, again demonstrating the central role of this receptor in relaying the effects of laminin.
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