Ghézali Grégory, Calvo Charles-Félix, Pillet Laure-Elise, Llense Flora, Ezan Pascal, Pannasch Ulrike, Bemelmans Alexis-Pierre, Etienne Manneville Sandrine, Rouach Nathalie
Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR 7241, INSERM U1050, Labex Memolife, PSL Research University, Paris 75005, France.
Doctoral School N°158, Pierre and Marie Curie University, Paris 75005, France.
Development. 2018 Feb 23;145(4):dev155275. doi: 10.1242/dev.155275.
Astrocytes undergo intense morphological maturation during development, changing from individual sparsely branched cells to polarized and tremendously ramified cells. Connexin 30, an astroglial gap-junction channel-forming protein expressed postnatally, regulates the extension and ramification of astroglial processes. However, the involvement of connexin 30 in astroglial polarization, which is known to control cell morphology, remains unexplored. We found that connexin 30, independently of gap-junction-mediated intercellular biochemical coupling, alters the orientation of astrocyte protrusion, centrosome and Golgi apparatus during polarized migration in an wound-healing assay. Connexin 30 sets the orientation of astroglial motile protrusions via modulation of the laminin/β1 integrin/Cdc42 polarity pathway. Connexin 30 indeed reduces laminin levels, inhibits the redistribution of the β1-integrin extracellular matrix receptors, and inhibits the recruitment and activation of the small Rho GTPase Cdc42 at the leading edge of migrating astrocytes. , connexin 30, the expression of which is developmentally regulated, also contributes to the establishment of hippocampal astrocyte polarity during postnatal maturation. This study thus reveals that connexin 30 controls astroglial polarity during development.
星形胶质细胞在发育过程中经历强烈的形态成熟，从单个分支稀疏的细胞转变为极化且分支繁多的细胞。连接蛋白30是一种出生后表达的星形胶质细胞间隙连接通道形成蛋白，它调节星形胶质细胞突起的延伸和分支。然而，连接蛋白30在已知可控制细胞形态的星形胶质细胞极化中的作用仍未得到探索。我们发现，在伤口愈合试验中，连接蛋白30在极化迁移过程中独立于间隙连接介导的细胞间生化偶联，改变星形胶质细胞突起、中心体和高尔基体的方向。连接蛋白30通过调节层粘连蛋白/β1整合素/Cdc42极性途径来设定星形胶质细胞运动突起的方向。连接蛋白30确实会降低层粘连蛋白水平，抑制β1整合素细胞外基质受体的重新分布，并抑制迁移的星形胶质细胞前沿小Rho GTP酶Cdc42的募集和激活。此外，其表达受发育调控的连接蛋白30也有助于出生后成熟过程中海马星形胶质细胞极性的建立。因此，这项研究揭示了连接蛋白30在发育过程中控制星形胶质细胞极性。
