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

Abstract	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.
Authors	Christopher J Noakes, Grace Lee, Martin Lowe
Journal	Molecular biology of the cell (Mol Biol Cell) Vol. 22 Issue 5 Pg. 606-23 (Mar 01 2011) ISSN: 1939-4586 [Electronic] United States
PMID	21233288 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	PHETA1 protein, human PHETA2 protein, human RNA, Small Interfering Receptors, Transferrin Vesicular Transport Proteins Shiga Toxin Hydrolases Phosphoric Monoester Hydrolases OCRL protein, human
Topics	Amino Acid Motifs Amino Acid Sequence Cell Membrane (metabolism) Conserved Sequence (genetics) Endocytosis Endosomes (metabolism) HeLa Cells Humans Hydrolases (metabolism) Lysosomes (enzymology) Molecular Sequence Data Mutation (genetics) Oculocerebrorenal Syndrome (enzymology, genetics) Phosphoric Monoester Hydrolases (metabolism) Protein Binding Protein Structure, Tertiary Protein Transport RNA, Small Interfering (metabolism) Receptors, Transferrin (metabolism) Secretory Pathway Shiga Toxin (metabolism) Vesicular Transport Proteins (chemistry, metabolism) trans-Golgi Network (metabolism)

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