Cellular and molecular function of mucolipins (TRPML) and polycystin 2 (TRPP2).
Mucolipins (transient receptor potential mucolipin, TRPML) and polycystin-2 proteins (transient receptor potential polycystin, TRPP) constitute two small families of cation channels with motif and sequence similarities to the transient receptor potential (TRP) class of non-selective cation channels. Genetic defects in TRPML1 and TRPML3 in humans and in animal models cause the accumulation of large vacuoles, leading to a variety of cellular phenotypes including neurological and neurosensory deficiencies. TRPML1 is a Ca(2+)-, K(+)-, and Na(+)-permeable cation channel sensitive to pH changes, and regulates a critical step in the maturation of late endosomes to lysosomes. Mutations of TRPP2 in humans result in autosomal dominant polycystic kidney disease. Molecular studies have demonstrated that TRPP2 and TRPP3 proteins function as Ca(2+)-regulated, non-selective cation channels. During embryogenesis TRPP2 is active in node monocilia and plays a role in the establishment of left-right asymmetry. Recent results have indicated that TRPP2 interacts with polycystin-1 and that their interaction is important for their function as mechanosensitive channels at the primary cilium of renal epithelial cells. The interaction of polycystin family members appears to be conserved and is critical for fertilization and mating behavior. An emerging concept from the studies of the polycystin family is that they function as cation-influx based devices for sensing extracellular signals on ciliated structures. Here we review the function of TRPML1 and TRPP2 as representative members of these families, focusing on the genetics, physiology, and biochemistry.
Qian
Feng
F
Division of Nephrology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA. fqjhupkd@jhmi.edu
Noben-Trauth
Konrad
K
D000818:Animals; D015220:Calcium Channels; D004195:Disease Models, Animal; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology; D008565:Membrane Proteins; D009081:Mucolipidoses / Q000503:physiopathology; D016891:Polycystic Kidney, Autosomal Dominant / Q000503:physiopathology; D050053:TRPM Cation Channels / Q000502:physiology*; D050396:TRPP Cation Channels; D050051:Transient Receptor Potential Channels / Q000502:physiology
D015220:Calcium Channels; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D050053:TRPM Cation Channels; D050396:TRPP Cation Channels; D050051:Transient Receptor Potential Channels; C416674:MCOLN1 protein, human; C510642:MCOLN3 protein, human; C510641:Mcoln2 protein, human; C511304:PKD2L2 protein, human