Laboratory of Molecular Neuroscience, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Post box 1105, Blindern, 0317 Oslo, Norway.
Laboratory of Molecular Neuroscience, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Post box 1105, Blindern, 0317 Oslo, Norway.
Biochim Biophys Acta Biomembr. 2021 Aug 1;1863(8):183616. doi: 10.1016/j.bbamem.2021.183616. Epub 2021 Apr 16.
Aquaporin-4 (AQP4) water channels and gap junction proteins (connexins) are two classes of astrocytic membrane proteins critically involved in brain water and ion homeostasis. AQP4 channels are anchored by α1-syntrophin to the perivascular astrocytic endfoot membrane domains where they control water flux at the blood-brain interface while connexins cluster at the lateral aspects of the astrocytic endfeet forming gap junctions that allow water and ions to dissipate through the astrocyte syncytium. Recent studies have pointed to an interdependence between astrocytic AQP4 and astrocytic gap junctions but the underlying mechanism remains to be explored. Here we use a novel transgenic mouse line to unravel whether β1-syntrophin (coexpressed with α1-syntrophin in astrocytic plasma membranes) is implicated in the expression of AQP4 isoforms and formation of gap junctions in brain. Our results show that while the effect of β1-syntrophin deletion is rather limited, double knockout of α1- and β1-syntrophin causes a downregulation of the novel AQP4 isoform AQP4ex and an increase in the number of astrocytic gap junctions. The present study highlight the importance of syntrophins in orchestrating specialized functional domains of brain astrocytes.
水通道蛋白-4（AQP4）和缝隙连接蛋白（连接蛋白）是两类与脑水和离子稳态密切相关的星形胶质细胞膜蛋白。AQP4 通道通过α1-肌联蛋白锚定于血管周围星形胶质细胞足突膜域，控制血脑界面的水通量，而连接蛋白在星形胶质细胞足突的侧方聚集形成缝隙连接，允许水和离子通过星形胶质细胞合胞体消散。最近的研究表明，星形胶质细胞 AQP4 和星形胶质细胞缝隙连接之间存在相互依赖性，但潜在的机制仍有待探索。在这里，我们使用一种新型转基因小鼠品系来阐明β1-肌联蛋白（与星形胶质细胞膜上的α1-肌联蛋白共同表达）是否参与脑内 AQP4 同工型的表达和缝隙连接的形成。我们的结果表明，虽然β1-肌联蛋白缺失的影响相当有限，但α1-和β1-肌联蛋白的双重敲除导致新型 AQP4 同工型 AQP4ex 的下调和星形胶质细胞缝隙连接数量的增加。本研究强调了肌联蛋白在协调脑星形胶质细胞特定功能域中的重要性。
