TRPpathies

Abstract

Many human diseases are caused by mutations in ion channels. Dissecting the pathogenesis of these 'channelopathies' has yielded important insights into the regulation of vital biological processes by ions and has become a productive tool of modern ion channel biology. One of the best examples of a synergism between the clinical and basic science aspects of a modern biological topic is cystic fibrosis. Not only did the identification of the ion channel mutated in cystic fibrosis pinpoint the root cause of this disease, but it also has significantly advanced our understanding of basic biological processes as diverse as protein folding and epithelial fluid and electrolyte secretion. The list of confirmed 'channelopathies' is growing and several members of the TRP family of ion channels have been implicated in human diseases such as mucolipidosis type IV (MLIV), autosomal dominant polycystic kidney disease (ADPKD), familial focal segmental glomerulosclerosis (FSG), hypomagnesemia with secondary hypocalcaemia (HSH), and several forms of cancer. Analysing pathogenesis of the diseases linked to TRP dysregulation provides an exciting means of identifying novel functions of TRP channels.

Planar Cell Polarity and the Kidney

“…[62][63][64][65][66][67][68][69][70][71][72][73][74][75] There are many forms of cystic kidney disease in human. 66 -71 Although many of the genes that are mutated in polycystic kidney disease (PKD) have been identified, the pathogenetic mechanisms initiating cyst formation are still unclear.…”

A novel mode of TRPML3 regulation by extracytosolic pH absent in the varitint-waddler phenotype

“…The TRPML subfamily has three members, TRPML1, TRPML2 and TRPML3. Mutations in TRPML1 cause the lysosomal storage disease mucolipidosis type IV (Bargal et al, 2000;Kiselyov et al, 2007). TRPML1 is a lysosomal channel (Manzoni et al, 2004) that when mutated or deleted impairs mainly lysosomal recycling (Fares and Greenwald, 2001;Hersh et al, 2002).…”

The intracellular Ca2+channels of membrane traffic

“…Limitations of these approaches have been discussed before. 66,67 siRNA-driven TRPML1 knockdown (KD) models 24,68 yielded pre-lysosomal membrane traffic delays in one model 68 and post-lysosomal delays with no pre-lysosomal delays in another study. 24 Localization of TRPML3 is broader than that of TRPML1 and it is expressed in all compartments of the endocytic pathway 38 (see also Fig.…”