RAegulation of glia number in drosophila by Rap/Fzr, an activator of the anaphase-promoting complex, and loco, an RGS protein
RAegulation of glia number in drosophila by Rap/Fzr, an activator of the anaphase-promoting complex, and loco, an RGS protein
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DOI：
10.1534/genetics.107.086397
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发表时间：
2008-04-01
期刊：
影响因子：
3.3
通讯作者：
Venkatesh, Tadmiri R.
中科院分区：
文献类型：
--
作者：
Kaplow, Margarita E.;Korayem, Adam H.;Venkatesh, Tadmiri R.
胶质细胞调节大量的细胞过程，对神经系统的发育和功能至关重要。尽管胶质细胞在神经生物学中具有巨大的重要性，但对它们的研究仍然很少，指导其分化的分子机制也知之甚少。RAP/FzR是哺乳动物CDH1的果蝇同源物，CDH1是后期促进复合体/环体(APC/C)的调节亚基。APC/C是一种E3泛素连接酶复合体，以其在细胞周期进程中的作用而闻名。在这项研究中，我们发现了Rap/Fzr的一个新的细胞角色。RAP/FZR功能丧失导致三龄幼虫神经系统神经胶质细胞数量显著增加。相反，在repo-GAL4的驱动下，UAS-RAP/FZR的异位表达导致胶质细胞急剧减少。利用MARCM技术进行克隆分析的数据表明，Rap/Fzr调控发育中的幼虫神经系统表面神经胶质细胞的分化。我们的遗传和生化数据进一步表明，Rap/Fzr通过与Loco相互作用来调节神经胶质细胞的分化，Loco是G蛋白信号转导(RGS)蛋白的调节者，也是已知的胶质细胞规范的效应者。我们认为Rap/Fzr靶向泛素化的Loco，从而调节发育中的神经系统中的神经胶质分化。
Glia mediate a vast array of cellular processes and are critical for nervous system development and function. Despite their immense importance in neurobiology, glia remain understudied and the molecular mechanisms that direct their differentiation are poorly understood. Rap/Fzr is the Drosophila homolog of the mammalian Cdh1, a regulatory subunit of the anaphase-promoting complex/cyclosome (APC/C). APC/C is an E3 ubiquitin ligase complex well characterized for its role in cell cycle progression. In this study, we have uncovered a novel cellular role for Rap/Fzr. Loss of rap/fzr function leads to a marked increase in the number of glia in the nervous system of third instar larvae. Conversely, ectopic expression of UAS-rap/fzr, driven by repo-GAL4, results in the drastic reduction of glia. Data from clonal analyses using the MARCM technique show that Rap/Fzr regulates the differentiation of surface glia in the developing larval nervous system. Our genetic and biochemical data further indicate that Rap/Fzr regulates glial differentiation through its interaction with Loco, a regulator of G-protein signaling (RGS) protein and a known effector of glia specification. We propose that Rap/Fzr targets Loco for ubiquitination, thereby regulating glial differentiation in the developing nervous system.