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Rab5 效应因子 Rabenosyn-5 在平面细胞极性中的新功能。

A novel function for the Rab5 effector Rabenosyn-5 in planar cell polarity.

机构信息

Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.

出版信息

Development. 2010 Jul;137(14):2353-64. doi: 10.1242/dev.048413. Epub 2010 Jun 9.

Abstract

In addition to apicobasal polarization, some epithelia also display polarity within the plane of the epithelium. To what extent polarized endocytosis plays a role in the establishment and maintenance of planar cell polarity (PCP) is at present unclear. Here, we investigated the role of Rabenosyn-5 (Rbsn-5), an evolutionarily conserved effector of the small GTPase Rab5, in the development of Drosophila wing epithelium. We found that Rbsn-5 regulates endocytosis at the apical side of the wing epithelium and, surprisingly, further uncovered a novel function of this protein in PCP. At early stages of pupal wing development, the PCP protein Fmi redistributes between the cortex and Rab5- and Rbsn-5-positive early endosomes. During planar polarization, Rbsn-5 is recruited at the apical cell boundaries and redistributes along the proximodistal axis in an Fmi-dependent manner. At pre-hair formation, Rbsn-5 accumulates at the bottom of emerging hairs. Loss of Rbsn-5 causes intracellular accumulation of Fmi and typical PCP alterations such as defects in cell packing, in the polarized distribution of PCP proteins, and in hair orientation and formation. Our results suggest that establishment of planar polarity requires the activity of Rbsn-5 in regulating both the endocytic trafficking of Fmi at the apical cell boundaries and hair morphology.

摘要

除了顶端-基底极性外,一些上皮细胞在其上皮层内也显示极性。极化内吞作用在平面细胞极性(PCP)的建立和维持中起多大作用目前尚不清楚。在这里,我们研究了 Rab5 小 GTPase 的保守效应物 Rabenosyn-5(Rbsn-5)在果蝇翅膀上皮细胞发育中的作用。我们发现 Rbsn-5 调节翅膀上皮细胞的顶端侧的内吞作用,并且令人惊讶的是,进一步揭示了该蛋白在 PCP 中的一个新功能。在蛹期翅膀发育的早期阶段,PCP 蛋白 Fmi 在皮层和 Rab5 和 Rbsn-5 阳性早期内体之间重新分布。在平面极化过程中,Rbsn-5 在上皮细胞顶端边界募集,并以 Fmi 依赖的方式沿近-远轴重新分布。在发状结构形成之前,Rbsn-5 积聚在新出现的毛发的底部。Rbsn-5 的缺失导致 Fmi 的细胞内积累以及典型的 PCP 改变,如细胞包装缺陷、PCP 蛋白的极化分布缺陷以及毛发方向和形成缺陷。我们的结果表明,平面极性的建立需要 Rbsn-5 活性来调节 Fmi 在顶端细胞边界的内吞作用和毛发形态。

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