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Exp Cell Res. 2011 Apr 1;317(6):691-705. doi: 10.1016/j.yexcr.2011.01.008. Epub 2011 Jan 20.

The cation channel mucolipin-1 is a bifunctional protein that facilitates membrane remodeling via its serine lipase domain.

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  • 1Division of Endocrinology, Diabetes and Hypertension and Membrane Biology Program, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. jlaplante@rics.bwh.harvard.edu

Abstract

Phospholipase modulators have been shown to affect the topology of lipid bilayers and the formation of tubulo-vesicular structures, but the specific endogenous phospholipases involved have yet to be identified. Here we show that TRPML1 (MLN1), a Ca(2+)-permeable channel, contributes to membrane remodeling through a serine lipase consensus domain, and thus represents a novel type of bifunctional protein. Remarkably, this serine lipase active site determines the ability of MLN1 to generate tubulo-vesicular extensions in mucolipin-1-expressing oocytes, human fibroblasts and model membrane vesicles. Our demonstration that MLN1 is involved in membrane remodeling and the formation of extensions suggests that it may play a role in the formation of cellular processes linked to the late endosome/lysosome (LE/L) pathway. MLN1 is absent or mutated in patients with mucolipidosis IV (MLIV), a lysosomal disorder with devastating neurological and other consequences. This study provides potential insight into the pathophysiology of MLIV.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:
21256127
[PubMed - indexed for MEDLINE]
PMCID:
PMC3103141
Free PMC Article

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