Department of Developmental Biology, Washington University in St. Louis, St. Louis, MO 63110, USA.
J Cell Biol. 2010 Mar 8;188(5):717-34. doi: 10.1083/jcb.200911126. Epub 2010 Mar 1.
Endosomal maturation is critical for accurate and efficient cargo transport through endosomal compartments. Here we identify a mutation of the novel Drosophila gene, ema (endosomal maturation defective) in a screen for abnormal synaptic overgrowth and defective protein trafficking. Ema is an endosomal membrane protein required for trafficking of fluid-phase and receptor-mediated endocytic cargos. In the ema mutant, enlarged endosomal compartments accumulate as endosomal maturation fails, with early and late endosomes unable to progress into mature degradative late endosomes and lysosomes. Defective endosomal down-regulation of BMP signaling is responsible for the abnormal synaptic overgrowth. Ema binds to and genetically interacts with Vps16A, a component of the class C Vps-HOPS complex that promotes endosomal maturation. The human orthologue of ema, Clec16A, is a candidate susceptibility locus for autoimmune disorders, and its expression rescues the Drosophila mutant demonstrating conserved function. Characterizing this novel gene family identifies a new component of the endosomal pathway and provides insights into class C Vps-HOPS complex function.
内体成熟对于通过内体隔室进行准确和有效的货物运输至关重要。在这里，我们在筛选异常突触过度生长和蛋白质运输缺陷的过程中，鉴定出了一个新的果蝇基因 ema（内体成熟缺陷）的突变。Ema 是一种内体膜蛋白，对于液相等受体介导的内吞货物的运输是必需的。在 ema 突变体中，由于内体成熟失败，扩大的内体隔室积累，早期和晚期内体无法进展为成熟的降解性晚期内体和溶酶体。内体下调 BMP 信号的缺陷是导致异常突触过度生长的原因。Ema 与 Vps16A 结合，并与 Vps-HOPS 复合物的 C 类的一个组成部分发生遗传相互作用，该复合物促进内体成熟。ema 的人类同源物 Clec16A 是自身免疫性疾病的候选易感基因座，其表达挽救了果蝇突变体，表明其具有保守功能。该新基因家族的特征确定了内体途径的一个新组成部分，并提供了对 C 类 Vps-HOPS 复合物功能的深入了解。
