Polycystins: polymodal receptor/ion-channel cellular sensors.

Transient receptor potential (TRP) channel proteins are divided into seven subgroups that are currently designated as TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPN (NOMP-C, from no mechanoreceptor potential-C), TRPA (ankyrin-like with transmembrane domains 1) and TRPP (polycystin). TRPC, TRPV and TRPM are related to canonical TRP proteins whereas TRPN, TRPA and TRPP (polycystin) are more divergent. Most TRP channels are linked to sensory stimuli, including phototransduction, thermosensation and mechanosensation. The TRPP subfamily was named after its founding member, polycystin kidney disease-2 (PKD2), a gene product mutated in many cases of autosomal dominant polycystic kidney disease (ADPKD). ADPKD is a major inherited nephropathy, affecting over 1:1,000 of the worldwide population, characterized by the progressive development of fluid-filled cysts from the tubules and collecting ducts of affected kidneys. Loss-of-function mutations in either polycystin-2, a non-selective cation channel, or polycystin-1 (PKD1), a large plasma membrane integral protein, give rise to ADPKD. PKD1 and PKD2 are thought to function together as part of a multiprotein receptor/ion-channel complex or independently and may be involved in transducing Ca(2+)-dependent mechanosensitive signals in response to cilia bending in renal epithelial cells and endodermally derived cells. Further information on the growing number and physiological properties of these TRP-polycystins is the basis of this review.