Lysosomal Ca(2+) homeostasis: role in pathogenesis of lysosomal storage diseases.

Journal article

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: Lloyd-Evans, E; Platt, F

• Publication status: Published
• Journal: Cell calcium More from this journal
• Volume: 50
• Issue: 2
• Pages: 200-205
• Publication date: 2011-08-01
• DOI: 10.1016/j.ceca.2011.03.010
• EISSN: 1532-1991
• ISSN: 0143-4160
• Language: English
• Keywords: Lysosomes; Calcium Signaling; Homeostasis; Lysosomal Storage Diseases; NADP; Endosomes; Intracellular Membranes; Niemann-Pick Disease, Type C; Transient Receptor Potential Channels; TRPM Cation Channels; Mucolipidoses; Endocytosis; Humans; Chediak-Higashi Syndrome; Sphingosine