OCRL1 engages with the F-BAR protein pacsin 2 to promote biogenesis of membrane-trafficking intermediates.

Abstract

Mutation of the inositol 5-phosphatase OCRL1 causes Lowe syndrome and Dent-2 disease. Loss of OCRL1 function perturbs several cellular processes, including membrane traffic, but the underlying mechanisms remain poorly defined. Here we show that OCRL1 is part of the membrane-trafficking machinery operating at the trans-Golgi network (TGN)/endosome interface. OCRL1 interacts via IPIP27A with the F-BAR protein pacsin 2. OCRL1 and IPIP27A localize to mannose 6-phosphate receptor (MPR)-containing trafficking intermediates, and loss of either protein leads to defective MPR carrier biogenesis at the TGN and endosomes. OCRL1 5-phosphatase activity, which is membrane curvature sensitive, is stimulated by IPIP27A-mediated engagement of OCRL1 with pacsin 2 and promotes scission of MPR-containing carriers. Our data indicate a role for OCRL1, via IPIP27A, in regulating the formation of pacsin 2-dependent trafficking intermediates and reveal a mechanism for coupling PtdIns(4,5)P2 hydrolysis with carrier biogenesis on endomembranes.

• Authors: Peter G Billcliff, Christopher J Noakes, Zenobia B Mehta, Guanhua Yan, LokHang Mak, Rudiger Woscholski, Martin Lowe
• Journal: Molecular biology of the cell (Mol Biol Cell) Vol. 27 Issue 1 Pg. 90-107 (Jan 01 2016) ISSN: 1939-4586 [Electronic] United States
• PMID: 26510499 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 Billcliff, Noakes, Mehta, 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).

Chemical References

• Adaptor Proteins, Signal Transducing
• Nerve Tissue Proteins
• PACSIN2 protein, human
• Phosphatidylinositols
• Receptor, IGF Type 2
• SCRN1 protein, human
• Phosphoric Monoester Hydrolases
• OCRL protein, human
• Inositol Polyphosphate 5-Phosphatases

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Animals
• COS Cells
• Endocytosis
• Endosomes (metabolism)
• Genetic Diseases, X-Linked (genetics, metabolism, pathology)
• HEK293 Cells
• HeLa Cells
• Humans
• Inositol Polyphosphate 5-Phosphatases
• Nephrolithiasis (genetics, metabolism, pathology)
• Nerve Tissue Proteins (metabolism)
• Oculocerebrorenal Syndrome (genetics, metabolism, pathology)
• Phosphatidylinositols (biosynthesis, metabolism)
• Phosphoric Monoester Hydrolases (genetics, metabolism)
• Protein Transport
• Receptor, IGF Type 2 (metabolism)
• trans-Golgi Network (metabolism)