title: Lysosomal Ca(2+) homeostasis: role in pathogenesis of lysosomal storage diseases.
abstract: Disrupted cellular Ca(2+) signaling is believed to play a role in a number of human diseases including lysosomal storage diseases (LSD). LSDs are a group of ∼50 diseases caused predominantly by mutations in lysosomal proteins that result in accumulation of macromolecules within the lysosome. We recently reported that Niemann-Pick type C (NPC) is the first human disease to be associated with defective lysosomal Ca(2+) uptake and defective NAADP-mediated lysosomal Ca(2+) release. These defects in NPC cells leads to the disruption in endocytosis and subsequent lipid storage that is a feature of this disease. In contrast, Chediak-Higashi Syndrome cells have been reported to have enhanced lysosomal Ca(2+) uptake whilst the TRPML1 protein defective in mucolipidosis type IV is believed to function as a Ca(2+) channel. In this review we provide a summary of the current knowledge on the role of lysosomal Ca(2+) signaling in the pathogenesis of this group of diseases.
authors: School of Biosciences, Biomedical Sciences Building, Cardiff University, Museum Avenue, Cardiff CF10 3AX, United Kingdom. Lloyd-EvansE@cardiff.ac.uk
authors: Emyr
authors: E
authors: Lloyd-Evans
authors: Frances M
authors: FM
authors: Platt
mesh_terms: D020013:Calcium Signaling; D002609:Chediak-Higashi Syndrome / Q000378:metabolism / Q000473:pathology; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D016464:Lysosomal Storage Diseases / Q000378:metabolism / Q000473:pathology*; D008247:Lysosomes / Q000378:metabolism*; D009081:Mucolipidoses / Q000378:metabolism / Q000473:pathology; D009249:NADP / Q000031:analogs & derivatives / Q000378:metabolism; D052556:Niemann-Pick Disease, Type C / Q000378:metabolism / Q000473:pathology; D013110:Sphingosine / Q000378:metabolism; D050053:TRPM Cation Channels / Q000378:metabolism; D050051:Transient Receptor Potential Channels
chemical_list: C416674:MCOLN1 protein, human; D050053:TRPM Cation Channels; D050051:Transient Receptor Potential Channels; D009249:NADP; C024376:NAADP; D013110:Sphingosine