Valentine Meagan, Hogan Justin, Collier Simon
Department of Biomedical Sciences, Marshall University, Huntington, West Virginia.
Dev Dyn. 2014 Aug;243(8):977-87. doi: 10.1002/dvdy.24140. Epub 2014 May 6.
Receptor down-regulation by the multivesicular body (MVB) pathway is critical for many cellular signaling events. MVB generation is mediated by the highly conserved ESCRT (0, I, II, and III) protein complexes. Chmp1 is an ESCRT-III component and a putative tumor suppressor in humans. However, published data on Chmp1 activity are conflicting and its role during tissue development is not well defined.
We investigated the function of Drosophila Chmp1 and found that it is an essential gene. In the wing, loss of Chmp1 activity causes a cell fate change from intervein to vein, and interactions between Chmp1 and Drosophila Epidermal Growth Factor Receptor (DER) regulators suggest that Chmp1 negatively regulates DER signaling. Chmp1 knockdown also decreases Blistered expression, which is repressed by DER signaling. We find that Chmp1 protein localizes to the late endosome in Drosophila embryos, which is consistent with its effects on DER signaling resulting from its function in the ESCRT-III complex.
Drosophila Chmp1 negatively regulates DER signaling, likely through its role in MVB formation. Loss of Chmp1 activity in the Drosophila wing induces a cell fate change from intervein to vein that should provide a useful tool for future studies of ESCRT protein activity.
多泡体（MVB）途径介导的受体下调对许多细胞信号转导事件至关重要。MVB的产生由高度保守的ESCRT（0、I、II和III）蛋白复合物介导。Chmp1是一种ESCRT-III组分，在人类中被认为是一种肿瘤抑制因子。然而，已发表的关于Chmp1活性的数据相互矛盾，其在组织发育过程中的作用也尚未明确界定。
我们研究了果蝇Chmp1的功能，发现它是一个必需基因。在翅膀中，Chmp1活性丧失会导致细胞命运从翅脉间细胞转变为翅脉细胞，并且Chmp1与果蝇表皮生长因子受体（DER）调节因子之间的相互作用表明Chmp1负向调节DER信号传导。敲低Chmp1也会降低被DER信号传导抑制的Blistered的表达。我们发现Chmp1蛋白定位于果蝇胚胎的晚期内体，这与其在ESCRT-III复合物中的功能对DER信号传导的影响一致。
果蝇Chmp1可能通过其在MVB形成中的作用负向调节DER信号传导。果蝇翅膀中Chmp1活性的丧失诱导了细胞命运从翅脉间细胞到翅脉细胞的转变，这应为未来ESCRT蛋白活性的研究提供一个有用的工具。
