CGC Bibliography Paper 5642

Towards understanding the polycystins.

Kaletta T, Van der Craen M, Van Geel A, Dewulf N, Bogaert T, Branden M, King KV, Buechner M, Barstead R, Hyink D, Li HP, Geng L, Burrow C, Wilson P

Medline:

12411744

Citation:

Nephron Experimental Nephrology 93: e9-e17 2003

Type:

ARTICLE

Genes:

him-5 lov-1 pkd-2

Abstract:

Autosomal dominant polycystic kidney disease (ADPKD) is a very common inherited disease caused by mutation in PKD1 or PKD2 genes characterized by progressive enlargement of fluid-filled cysts and loss of renal function [1]. Previous studies proposed a role for human polycystin-1 in renal morphogenesis acting as a matrix receptor in focal adhesions and for polycystin-2 as a putative calcium channel [2,3]. The genome of Caenorhabditis elegans contains 2 new members of the polycystin family: lov-1, the homolog for PKD1; and pkd-2, the homolog for PKD2 [4; this paper]. Mutation analysis in C. elegans showed similarly compromised male mating behaviors in all single and double lov-1 and pkd-2 mutants, indicating their participation in a single genetic pathway. Expression analysis localized LOV-1 and PKD-2 to the ends of sensory neurons in the head, consistent with functions as chemo- or mechanosensors. Human and C. elegans PKD1 and PKD2 homologs, transfected into mammalian renal epithelial cells, co-localized with paxillin in focal adhesions suggesting function in a single biological pathway. Based on the role of polycystins in C. elegans sensory neuron function and conservation of PKD pathways we suggest that polycystins act as sensors of the extracellular environment, initiating, via focal adhesion assemble, intracellular transduction events in neuronal or morphogenetic processes.