QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 23 October 2007
doi: 10.1242/jcs.014423

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: jcs.014423v1 120/22/3941    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Williams, C. Articles by Lowe, M. Search for Related Content PubMed PubMed Citation Articles by Williams, C. Articles by Lowe, M. Social Bookmarking                         What's this?

Targeting of the type II inositol polyphosphate 5-phosphatase INPP5B to the early secretory pathway

Faculty of Life Sciences, University of Manchester, The Michael Smith Building, Oxford Road, Manchester M13 9PT, UK

^* Author for correspondence (e-mail: martin.lowe{at}manchester.ac.uk)

Accepted 29 August 2007

The inositol polyphosphate 5-phosphatase INPP5B is closely related to the Lowe syndrome protein OCRL1, sharing a similar substrate specificity, domain organisation and an ability to compensate for loss of OCRL1 in knockout mice. The cellular localisation and functions of INPP5B have remained poorly defined until recently, when a role within the endocytic pathway was suggested. Here, we report that INPP5B is also localised to the early secretory pathway including the Golgi apparatus and ER-to-Golgi intermediate compartment (ERGIC). Consistent with this localisation, INPP5B binds to specific RAB proteins within the secretory pathway, and mutational analysis indicates that RAB binding is required for efficient Golgi targeting of INPP5B. Unlike OCRL1, INPP5B interacts with neither clathrin nor -adaptin and is largely absent from clathrin-coated intermediates. Expression of INPP5B but not OCRL1 alters the distribution of the cycling protein ERGIC53 when cells are incubated at low temperature (15°C) or in the presence of brefeldin A, causing ERGIC53 to accumulate in the ERGIC, with a concomitant loss from the ER. Our data suggest a role for INPP5B in retrograde ERGIC-to-ER transport and imply that it has functions distinct from those of OCRL1 within both the secretory and endocytic pathways.

Key words: Type II 5-phosphatase, INPP5B, Golgi apparatus, Intermediate compartment, Endosome, RAB

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				R. Choudhury, C. J. Noakes, E. McKenzie, C. Kox, and M. Lowe Differential Clathrin Binding and Subcellular Localization of OCRL1 Splice Isoforms J. Biol. Chem., April 10, 2009; 284(15): 9965 - 9973. [Abstract] [Full Text] [PDF]

				M. Fukuda, E. Kanno, K. Ishibashi, and T. Itoh Large Scale Screening for Novel Rab Effectors Reveals Unexpected Broad Rab Binding Specificity Mol. Cell. Proteomics, June 1, 2008; 7(6): 1031 - 1042. [Abstract] [Full Text] [PDF]