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The PH domain proteins IPIP27A and B link OCRL1 to receptor recycling in the endocytic pathway

Mutation of the inositol polyphosphate 5-phosphatase OCRL1 results in two disorders in humans, namely Lowe syndrome (characterized by ocular, nervous system, and renal defects) and type 2 Dent disease (in which only the renal symptoms are evident). The disease mechanisms of these syndromes are poorl...

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Detalles Bibliográficos
Autores principales: Noakes, Christopher J., Lee, Grace, Lowe, Martin
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046058/
https://www.ncbi.nlm.nih.gov/pubmed/21233288
http://dx.doi.org/10.1091/mbc.E10-08-0730
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author Noakes, Christopher J.
Lee, Grace
Lowe, Martin
author_facet Noakes, Christopher J.
Lee, Grace
Lowe, Martin
author_sort Noakes, Christopher J.
collection PubMed
description Mutation of the inositol polyphosphate 5-phosphatase OCRL1 results in two disorders in humans, namely Lowe syndrome (characterized by ocular, nervous system, and renal defects) and type 2 Dent disease (in which only the renal symptoms are evident). The disease mechanisms of these syndromes are poorly understood. Here we identify two novel OCRL1-binding proteins, termed inositol polyphosphate phosphatase interacting protein of 27 kDa (IPIP27)A and B (also known as Ses1 and 2), that also bind the related 5-phosphatase Inpp5b. The IPIPs bind to the C-terminal region of these phosphatases via a conserved motif similar to that found in the signaling protein APPL1. IPIP27A and B, which form homo- and heterodimers, localize to early and recycling endosomes and the trans-Golgi network (TGN). The IPIPs are required for receptor recycling from endosomes, both to the TGN and to the plasma membrane. Our results identify IPIP27A and B as key players in endocytic trafficking and strongly suggest that defects in this process are responsible for the pathology of Lowe syndrome and Dent disease.
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spelling pubmed-30460582011-05-16 The PH domain proteins IPIP27A and B link OCRL1 to receptor recycling in the endocytic pathway Noakes, Christopher J. Lee, Grace Lowe, Martin Mol Biol Cell Articles Mutation of the inositol polyphosphate 5-phosphatase OCRL1 results in two disorders in humans, namely Lowe syndrome (characterized by ocular, nervous system, and renal defects) and type 2 Dent disease (in which only the renal symptoms are evident). The disease mechanisms of these syndromes are poorly understood. Here we identify two novel OCRL1-binding proteins, termed inositol polyphosphate phosphatase interacting protein of 27 kDa (IPIP27)A and B (also known as Ses1 and 2), that also bind the related 5-phosphatase Inpp5b. The IPIPs bind to the C-terminal region of these phosphatases via a conserved motif similar to that found in the signaling protein APPL1. IPIP27A and B, which form homo- and heterodimers, localize to early and recycling endosomes and the trans-Golgi network (TGN). The IPIPs are required for receptor recycling from endosomes, both to the TGN and to the plasma membrane. Our results identify IPIP27A and B as key players in endocytic trafficking and strongly suggest that defects in this process are responsible for the pathology of Lowe syndrome and Dent disease. The American Society for Cell Biology 2011-03-01 /pmc/articles/PMC3046058/ /pubmed/21233288 http://dx.doi.org/10.1091/mbc.E10-08-0730 Text en © 2011 Noakes et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,“ “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Noakes, Christopher J.
Lee, Grace
Lowe, Martin
The PH domain proteins IPIP27A and B link OCRL1 to receptor recycling in the endocytic pathway
title The PH domain proteins IPIP27A and B link OCRL1 to receptor recycling in the endocytic pathway
title_full The PH domain proteins IPIP27A and B link OCRL1 to receptor recycling in the endocytic pathway
title_fullStr The PH domain proteins IPIP27A and B link OCRL1 to receptor recycling in the endocytic pathway
title_full_unstemmed The PH domain proteins IPIP27A and B link OCRL1 to receptor recycling in the endocytic pathway
title_short The PH domain proteins IPIP27A and B link OCRL1 to receptor recycling in the endocytic pathway
title_sort ph domain proteins ipip27a and b link ocrl1 to receptor recycling in the endocytic pathway
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046058/
https://www.ncbi.nlm.nih.gov/pubmed/21233288
http://dx.doi.org/10.1091/mbc.E10-08-0730
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