The Drosophila blood brain barrier is maintained by GPCR-dependent dynamic actin structures.

The Drosophila blood brain barrier is maintained by GPCR-dependent dynamic actin structures.
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DOI:
10.1083/jcb.201007095
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发表时间:
2011-01-24
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Volk T
Volk T
中科院分区:
其他
文献类型:
--
作者:
Hatan M;Shinder V;Israeli D;Schnorrer F;Volk T

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G 蛋白偶联受体 Moody 诱导并维持神经束膜下神经胶质细胞侧缘富含肌动蛋白的结构的形成。血脑屏障(BBB)对于神经系统与周围环境的隔离至关重要。在果蝇中,血脑屏障由神经束膜下神经胶质细胞 (SPG) 之间形成的隔膜连接维持,并且需要 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 细胞侧缘动态形成的新型专门富含肌动蛋白的结构 (ARS)。 ARS 的形成以及与非肌肉肌球蛋白的关联受 Moody/GPCR 信号传导调节,并且需要肌球蛋白激活。一致地,检测到 ARS 定位、Ca2+ 水平升高和肌球蛋白轻链磷酸化之间的重叠。通过抑制肌动蛋白调节剂 Arp2/3 复合物来破坏 ARS 会导致 BBB 的废除。我们的结果表明,果蝇 BBB 是通过依赖 Moody/GPCR 的 ARS 形成来维持的,而 ARS 的形成得到了肌球蛋白激活的支持。 ARS 靠近隔膜连接处的定位能够有效密封神经索生长过程中形成的膜间隙。
Formation of actin-rich structures along the lateral borders of subperineurial glial cells are induced and maintained by the G protein–coupled receptor Moody. 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 Ca2+ 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.
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