Wang Tuanlao, Hong Wanjin
Membrane Biology Laboratory, Institute of Molecular and Cell Biology, Proteos, 61 Biopolis Drive, Singapore 138673, Singapore.
Biochem Biophys Res Commun. 2006 Nov 17;350(2):413-23. doi: 10.1016/j.bbrc.2006.09.064. Epub 2006 Sep 25.
RILP is emerging as a key regulator of late endocytic pathway by functioning as a downstream effector of activated Rab7 and Rab34, while ESCRT-I-->ESCRT-II-->ESCRT-III machinery acts in sorting proteins to the multivesicular body (MVB) initiated at the early/sorting endosome. We show here that the early machinery is integrated with the late machinery through a novel regulatory loop in which RILP interacts with VPS22 and VPS36 of ESCRT-II to mediate their membrane recruitment. The N-terminal and C-terminal half of RILP mediate interaction with VPS22 and VPS36, respectively. Overexpression of RILP leads to enlarged and clustered MVBs marked by lysobisphosphatidic acid (LBPA). In addition, RILP or its C-terminal fragment causes a retardation of sorting internalized EGF to the degradation route at the level of sorting endosomes marked by EEA1. We propose that RILP-->ESCRT-II serves as a regulatory/feedback loop to govern the coordination of early and late parts of the endocytic pathway.
RILP正作为晚期内吞途径的关键调节因子崭露头角，它作为活化的Rab7和Rab34的下游效应物发挥作用，而ESCRT-I→ESCRT-II→ESCRT-III机制则在将蛋白质分选到起始于早期/分选内体的多泡体（MVB）中发挥作用。我们在此表明，早期机制通过一个新的调节环与晚期机制整合，其中RILP与ESCRT-II的VPS22和VPS36相互作用，介导它们向膜的募集。RILP的N端和C端分别介导与VPS22和VPS36的相互作用。RILP的过表达导致以溶血双磷脂酸（LBPA）为标记的MVB增大并聚集。此外，RILP或其C端片段在以EEA1为标记的分选内体水平上导致内化的表皮生长因子（EGF）向降解途径的分选延迟。我们提出，RILP→ESCRT-II作为一个调节/反馈环来控制内吞途径早期和晚期部分的协调。
