title: Polycystins and intercellular mechanotransduction: A precise dosage of polycystin 2 is necessary for alpha-actinin reinforcement of junctions upon mechanical stimulation.
abstract: Polycystins 1 and 2, which are mutated in Autosomal Polycystic Kidney Disease, are involved in mechanotransduction through various mechanisms. In renal cells, polycystins not only have an important mechanotransductive role in primary cilia but are also present in intercellular contacts but their role there remains unclear. Here, we address the hypothesis that polycystins are involved in mechanotransduction via intercellular junctions, which would be expected to have consequences on tissue organization. We focused on the role of polycystin 2, which could be involved in mechanical organization at junctions either by its channel activity or by the direct recruitment of cytoskeleton components such as the F-actin cross-linker α-actinin. After mechanical stimulation of intercellular junctions in MDCK renal epithelial cells, α-actinin is rapidly recruited but this is inhibited upon overexpression of PC2 or the D509V mutant that lacks channel activity, and is also decreased upon PC2 silencing. This suggests that a precise dosage of PC2 is necessary for an adequate mechanosensitive α-actinin recruitment at junctions. At the multicellular level, a change in PC2 expression was associated with changes in velocity in confluent epithelia and during wound healing together with a loss of orientation. This study suggests that the mechanosensitive regulation of cytoskeleton by polycystins in intercellular contacts may be important in the context of ADPKD.
authors: Laboratoire Physico Chimie Curie, Institut Curie, Paris Sciences et Lettres Research University, Centre National de la Recherche Scientifique UMR 168, 75005 Paris, France; Sorbonne Universités, UPMC University Paris 06, 75005 Paris, France.
authors: Laxsoomee
authors: L
authors: Bhoonderowa
authors: Laboratoire Physico Chimie Curie, Institut Curie, Paris Sciences et Lettres Research University, Centre National de la Recherche Scientifique UMR 168, 75005 Paris, France; Sorbonne Universités, UPMC University Paris 06, 75005 Paris, France.
authors: Fatima
authors: F
authors: Hameurlaine
authors: Laboratoire Physico Chimie Curie, Institut Curie, Paris Sciences et Lettres Research University, Centre National de la Recherche Scientifique UMR 168, 75005 Paris, France; Sorbonne Universités, UPMC University Paris 06, 75005 Paris, France.
authors: Atousa
authors: A
authors: Arbabian
authors: Laboratoire Physico Chimie Curie, Institut Curie, Paris Sciences et Lettres Research University, Centre National de la Recherche Scientifique UMR 168, 75005 Paris, France; Sorbonne Universités, UPMC University Paris 06, 75005 Paris, France.
authors: Fahima
authors: F
authors: Faqir
authors: Laboratoire Physico Chimie Curie, Institut Curie, Paris Sciences et Lettres Research University, Centre National de la Recherche Scientifique UMR 168, 75005 Paris, France; Sorbonne Universités, UPMC University Paris 06, 75005 Paris, France.
authors: François
authors: F
authors: Amblard
authors: Laboratoire Physico Chimie Curie, Institut Curie, Paris Sciences et Lettres Research University, Centre National de la Recherche Scientifique UMR 168, 75005 Paris, France; Sorbonne Universités, UPMC University Paris 06, 75005 Paris, France. Electronic address: Sylvie.Coscoy@curie.fr.
authors: Sylvie
authors: S
authors: Coscoy
mesh_terms: D000185:Actinin / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement; D004285:Dogs; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism*; D061985:Madin Darby Canine Kidney Cells; D040542:Mechanotransduction, Cellular; D013314:Stress, Mechanical; D050396:TRPP Cation Channels / Q000378:metabolism*
chemical_list: D000185:Actinin; D002118:Calcium; D050396:TRPP Cation Channels
keywords: Alpha-actinin; Cell junction; Cytoskeleton; Epithelial cells; Ion channel; Mechanotransduction; Polycystin