期刊
DEVELOPMENTAL CELL
卷 13, 期 3, 页码 377-390出版社
CELL PRESS
DOI: 10.1016/j.devcel.2007.08.004
关键词
-
资金
- NCI NIH HHS [CA46128, P01 CA046128] Funding Source: Medline
- NIDA NIH HHS [DA018343, P30 DA018343] Funding Source: Medline
- NIDDK NIH HHS [P30 DK045735, DK45735, P30 DK045735-119008] Funding Source: Medline
- NIGMS NIH HHS [5T32GM07205, T32 GM007205] Funding Source: Medline
- NINDS NIH HHS [R01 NS036251-04, R37 NS036251, R01 NS036251-06, R01 NS036251-03, R01 NS036251-07, R01 NS036251-11, R01 NS036251-10, R01 NS036251-08, R01 NS036251, NS36251, R01 NS036251-05, R01 NS036251-09] Funding Source: Medline
Mutations in the inositol 5-phosphatase OCRL are responsible for Lowe syndrome, whose manifestations include mental retardation and renal Fanconi syndrome. OCRL has been implicated in membrane trafficking, but disease mechanisms remain unclear. We show that OCRL visits late-stage, endocytic clathrin-coated pits and binds the Rab5 effector APPL1 on peripheral early endosomes. The interaction with APPL1, which is mediated by the ASH-RhoGAP-like domains of OCRL and is abolished by disease mutations, provides a link to protein networks implicated in the re-absorptive function of the kidney and in the trafficking and signaling of growth factor receptors in the brain. Crystallographic studies reveal a role of the ASH-RhoGAP-like domains in positioning the phosphatase domain at the membrane interface and a clathrin box protruding from the RhoGAP-like domain. Our results support a role of OCRL in the early endocytic pathway, consistent with the predominant localization of its preferred substrates, PI(4,5)P-2 and PI(3,4,5)P-3, at the cell surface.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据