Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
J Cell Biol. 2011 Jan 24;192(2):307-19. doi: 10.1083/jcb.201007095. Epub 2011 Jan 17.
The blood brain barrier (BBB) is essential for insulation of the nervous system from the surrounding environment. In Drosophila melanogaster, the BBB is maintained by septate junctions formed between subperineurial glia (SPG) and requires the Moody/G protein-coupled receptor (GPCR) signaling pathway. In this study, we describe novel specialized actin-rich structures (ARSs) that dynamically form along the lateral borders of the SPG cells. ARS formation and association with nonmuscle myosin is regulated by Moody/GPCR signaling and requires myosin activation. Consistently, an overlap between ARS localization, elevated Ca(2+) levels, and myosin light chain phosphorylation is detected. Disruption of the ARS by inhibition of the actin regulator Arp2/3 complex leads to abrogation of the BBB. Our results suggest a mechanism by which the Drosophila BBB is maintained by Moody/GPCR-dependent formation of ARSs, which is supported by myosin activation. The localization of the ARSs close to the septate junctions enables efficient sealing of membrane gaps formed during nerve cord growth.
血脑屏障(BBB)对于神经系统与周围环境的隔离至关重要。在黑腹果蝇中,BBB 由位于神经鞘下胶质细胞(SPG)之间的隔膜连接形成,并需要 Moody/G 蛋白偶联受体(GPCR)信号通路。在这项研究中,我们描述了沿着 SPG 细胞的侧向边界动态形成的新型特殊的富含肌动蛋白的结构(ARS)。ARS 的形成和与非肌肉肌球蛋白的关联受 Moody/GPCR 信号的调节,并需要肌球蛋白的激活。一致地,ARS 的定位、Ca(2+)水平的升高和肌球蛋白轻链磷酸化之间存在重叠。通过抑制肌动蛋白调节蛋白 Arp2/3 复合物来破坏 ARS 会导致 BBB 的破坏。我们的结果表明,果蝇 BBB 通过 Moody/GPCR 依赖性的 ARS 形成来维持,这一过程得到了肌球蛋白激活的支持。ARS 的定位靠近隔膜连接,使在神经索生长过程中形成的膜间隙能够有效地密封。