期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 369, 期 2, 页码 493-499出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2008.02.067
关键词
OCRL; Lowe syndrome; APPL1; Rab5; endosome; oculocerebrorenal syndrome of Lowe
资金
- Howard Hughes Medical Institute Funding Source: Medline
- NIDDK NIH HHS [P50 DK057328, P30 DK045735, P50-DK57328, DK45735] Funding Source: Medline
- NIGMS NIH HHS [5T32GM07205, T32 GM007205] Funding Source: Medline
- NINDS NIH HHS [R37 NS036251, R01 NS036251, NS36251] Funding Source: Medline
Mutations in the inositol 5-phosphatase OCRL are responsible for Lowe syndrome, an X-linked disorder characterized by bilateral cataracts, mental retardation, neonatal hypotonia, and renal Fanconi syndrome, and for Dent disease, another X-linked condition characterized by kidney reabsorption defects. We have previously described an interaction of OCRL with the endocytic adaptor APPL1 that links OCRL to protein networks involved in the disease phenotype. Here, we provide new evidence showing that among the interactions which target OCRL to membranes of the endocytic pathway, binding to APPL1 is the only one abolished by all known disease-causing missense mutations in the ASH-RhoGAP domains of the protein. Furthermore, we demonstrate that APPL1 and rab5 independently contribute to recruit OCRL to enlarged endosomes induced by the expression of constitutively active Rab5. Thus, binding to APPL1 helps localize OCRL at specific cellular sites, and disruption of this interaction may play a role in disease. (C) 2008 Elsevier Inc. All rights reserved.
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