title: Towards understanding the polycystins.
abstract: Autosomal dominant polycystic kidney disease (ADPKD) is a very common inherited disease caused by mutations 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 male tails and to the tips of CEM 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 the conservation of PKD pathways we suggest that polycystins act as sensors of the extracellular environment, initiating, via focal adhesion assembly, intracellular transduction events in neuronal or morphogenetic processes.
authors.affiliation: Devgen N.V, Zwijnaarde, Belgium.
authors.forename: Titus
authors.initials: T
authors.lastname: Kaletta
authors.forename: Marc
authors.initials: M
authors.lastname: Van der Craen
authors.forename: Anton
authors.initials: A
authors.lastname: Van Geel
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dewulf
authors.forename: Thierry
authors.initials: T
authors.lastname: Bogaert
authors.forename: Michael
authors.initials: M
authors.lastname: Branden
authors.forename: Kevin V
authors.initials: KV
authors.lastname: King
authors.forename: Matthew
authors.initials: M
authors.lastname: Buechner
authors.forename: Robert
authors.initials: R
authors.lastname: Barstead
authors.forename: Deborah
authors.initials: D
authors.lastname: Hyink
authors.forename: Hsi-Ping
authors.initials: HP
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Geng
authors.forename: Christopher
authors.initials: C
authors.lastname: Burrow
authors.forename: Patricia
authors.initials: P
authors.lastname: Wilson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D017238:Genes, Helminth / Q000235:genetics; D016678:Genome; D006801:Humans; D007668:Kidney; D018374:LLC-PK1 Cells / Q000737:chemistry; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D009475:Neurons, Afferent / Q000378:metabolism; D016891:Polycystic Kidney, Autosomal Dominant / Q000378:metabolism*; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D012689:Sequence Homology, Nucleic Acid; D012726:Sexual Behavior, Animal / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013552:Swine; D050396:TRPP Cation Channels
chemical_list: D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; D011506:Proteins; D050396:TRPP Cation Channels