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Exp Cell Res
2011 Apr 01;3176:691-705. doi: 10.1016/j.yexcr.2011.01.008.
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The cation channel mucolipin-1 is a bifunctional protein that facilitates membrane remodeling via its serine lipase domain.
LaPlante JM
,
Falardeau JL
,
Brown EM
,
Slaugenhaupt SA
,
Vassilev PM
.
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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.
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Altarescu,
The neurogenetics of mucolipidosis type IV.
2002, Pubmed
Altarescu,
The neurogenetics of mucolipidosis type IV.
2002,
Pubmed
Bach,
Abnormal ganglioside accumulation in cultured fibroblasts from patients with mucolipidosis IV.
1975,
Pubmed
Bach,
Mucopolysaccharide accumulation in cultured skin fibroblasts derived from patients with mucolipidosis IV.
1977,
Pubmed
Bach,
Lysosomal accumulation of phospholipids in mucolipidosis IV cultured fibroblasts.
1988,
Pubmed
Barbieri,
Characterization of Rab5:Q79L-stimulated endosome fusion.
1996,
Pubmed
Bargal,
Phospholipids accumulation in mucolipidosis IV cultured fibroblasts.
1988,
Pubmed
Bargal,
Mucolipidosis type IV: abnormal transport of lipids to lysosomes.
1997,
Pubmed
Bargal,
Identification of the gene causing mucolipidosis type IV.
2000,
Pubmed
Bassi,
Cloning of the gene encoding a novel integral membrane protein, mucolipidin-and identification of the two major founder mutations causing mucolipidosis type IV.
2000,
Pubmed
Berman,
Congenital corneal clouding with abnormal systemic storage bodies: a new variant of mucolipidosis.
1974,
Pubmed
Blackwood,
PLA2 promotes fusion between PMN-specific granules and complex liposomes.
1996,
Pubmed
Brown,
Phospholipase A2 (PLA2) enzymes in membrane trafficking: mediators of membrane shape and function.
2003,
Pubmed
Carpenter,
CellProfiler: image analysis software for identifying and quantifying cell phenotypes.
2006,
Pubmed
Chen,
Polycystin-L is a calcium-regulated cation channel permeable to calcium ions.
1999,
Pubmed
,
Xenbase
Cohen,
Phospholipases stimulate secretion in RBL mast cells.
2001,
Pubmed
Dargan,
Modulation of type-1 Ins(1,4,5)P3 receptor channels by the FK506-binding protein, FKBP12.
2002,
Pubmed
Farber,
Genetic analysis of digestive physiology using fluorescent phospholipid reporters.
2001,
Pubmed
Fares,
Regulation of endocytosis by CUP-5, the Caenorhabditis elegans mucolipin-1 homolog.
2001,
Pubmed
Galkina,
Inhibition of neutrophil spreading during adhesion to fibronectin reveals formation of long tubulovesicular cell extensions (cytonemes).
2001,
Pubmed
Gerasimenko,
Membrane repair: Ca(2+)-elicited lysosomal exocytosis.
2001,
Pubmed
Gerdes,
Tunneling nanotubes: a new route for the exchange of components between animal cells.
2007,
Pubmed
Gould,
The Trojan exosome hypothesis.
2003,
Pubmed
Holopainen,
Vectorial budding of vesicles by asymmetrical enzymatic formation of ceramide in giant liposomes.
2000,
Pubmed
Holopainen,
Macroscopic consequences of the action of phospholipase C on giant unilamellar liposomes.
2002,
Pubmed
Huttner,
Membrane curvature: a case of endofeelin' ..
2002,
Pubmed
Kim,
Identification of a human cDNA clone for lysosomal type Ca2+-independent phospholipase A2 and properties of the expressed protein.
1997,
Pubmed
,
Xenbase
Kiselyov,
TRP-ML1 is a lysosomal monovalent cation channel that undergoes proteolytic cleavage.
2005,
Pubmed
Kooijman,
Spontaneous curvature of phosphatidic acid and lysophosphatidic acid.
2005,
Pubmed
LaPlante,
Identification and characterization of the single channel function of human mucolipin-1 implicated in mucolipidosis type IV, a disorder affecting the lysosomal pathway.
2002,
Pubmed
,
Xenbase
LaPlante,
Functional links between mucolipin-1 and Ca2+-dependent membrane trafficking in mucolipidosis IV.
2004,
Pubmed
,
Xenbase
LaPlante,
Lysosomal exocytosis is impaired in mucolipidosis type IV.
2006,
Pubmed
,
Xenbase
Lamprecht,
CellProfiler: free, versatile software for automated biological image analysis.
2007,
Pubmed
Manzoni,
Overexpression of wild-type and mutant mucolipin proteins in mammalian cells: effects on the late endocytic compartment organization.
2004,
Pubmed
Mayorga,
Inhibition of endosome fusion by phospholipase A2 (PLA2) inhibitors points to a role for PLA2 in endocytosis.
1993,
Pubmed
Mayorga,
Calcium-dependent fusion among endosomes.
1994,
Pubmed
McMahon,
Membrane curvature and mechanisms of dynamic cell membrane remodelling.
2005,
Pubmed
Mukherjee,
Endocytic sorting of lipid analogues differing solely in the chemistry of their hydrophobic tails.
1999,
Pubmed
Nagao,
Ca(2+)-independent fusion of secretory granules with phospholipase A2-treated plasma membranes in vitro.
1995,
Pubmed
Nishio,
Ca(2+)-independent fusion of synaptic vesicles with phospholipase A2-treated presynaptic membranes in vitro.
1996,
Pubmed
Onfelt,
Can membrane nanotubes facilitate communication between immune cells?
2004,
Pubmed
Prody,
Purification and characterization of an N-acetyl-beta-D-glucosaminidase from cortical granules of Xenopus laevis eggs.
1985,
Pubmed
,
Xenbase
Pryor,
Mucolipin-1 is a lysosomal membrane protein required for intracellular lactosylceramide traffic.
2006,
Pubmed
Ramírez-Weber,
Cytonemes: cellular processes that project to the principal signaling center in Drosophila imaginal discs.
1999,
Pubmed
Raychowdhury,
Molecular pathophysiology of mucolipidosis type IV: pH dysregulation of the mucolipin-1 cation channel.
2004,
Pubmed
Reddy,
Plasma membrane repair is mediated by Ca(2+)-regulated exocytosis of lysosomes.
2001,
Pubmed
Rodríguez,
Lysosomes behave as Ca2+-regulated exocytic vesicles in fibroblasts and epithelial cells.
1997,
Pubmed
Rustom,
Nanotubular highways for intercellular organelle transport.
2004,
Pubmed
Schmidt,
Endophilin I mediates synaptic vesicle formation by transfer of arachidonate to lysophosphatidic acid.
1999,
Pubmed
Sheetz,
Biological membranes as bilayer couples. A molecular mechanism of drug-erythrocyte interactions.
1974,
Pubmed
Soyombo,
TRP-ML1 regulates lysosomal pH and acidic lysosomal lipid hydrolytic activity.
2006,
Pubmed
Staneva,
Phospholipase A2 promotes raft budding and fission from giant liposomes.
2004,
Pubmed
Sun,
Mucolipidosis type IV is caused by mutations in a gene encoding a novel transient receptor potential channel.
2000,
Pubmed
Vassilev,
Single-channel activities of the human epithelial Ca2+ transport proteins CaT1 and CaT2.
2001,
Pubmed
,
Xenbase
Vassilev,
Ca2+ channels from brain microsomal membranes reconstituted in patch-clamped bilayers.
1987,
Pubmed
Vassilev,
Reconstitution of membrane molecular mechanisms in bilayer lipid membranes and patch-clamp bilayers.
1989,
Pubmed
de Figueiredo,
Evidence that phospholipase A2 activity is required for Golgi complex and trans Golgi network membrane tubulation.
1998,
Pubmed
