title: Effect of hydro-osmotic pressure on polycystin-2 channel function in the human syncytiotrophoblast.
abstract: Polycystin-2 (PC2), one of the gene products whose mutations cause autosomal dominant polycystic kidney disease is a transient receptor potential (TRP)-type (TRPP2) Ca(2+)-permeable, non-selective cation channel. PC2 is localized in the plasma membrane, the primary cilium, and other cellular organelles of renal epithelial and other cells. Recent studies indicate that PC2 is involved in signal transduction events associated with the transient increase in cytosolic Ca(2+). Proof of evidence now hinges on involvement of the PC2 channel in the transduction of environmental signals. PC2 is abundantly expressed in the apical membrane of human syncytiotrophoblast (hST), a highly intricate epithelial tissue, which is essential for the maternal-fetal transfer of solutes, including ions. Physical forces such as hydrostatic (H) and osmotic (Pi) pressure play important roles in placenta homeostasis. In this study, we provide new information on PC2 channel regulation in the hST by these environmental factors, and propose a model as to how they may trigger the activation of PC2. Using apical hST vesicles reconstituted in a lipid bilayer system, we found that a change in either H or Pi modified PC2 channel activity. This stimulatory effect was no longer observed in hST vesicles pre-treated with the actin cytoskeleton disrupter cytochalasin D. As shown by immunofluorescence analysis PC2 co-localized with actin filaments in the vicinity of the plasma membrane. This co-localization was disrupted by cytochalasin D. Taken together, our findings indicate that physical forces exerted on cells regulate PC2 channel activity by a sensory mechanism involving the actin cytoskeleton.
authors: Laboratorio de Canales Iónicos, Departamento de Fisicoquímica y Química Analítica, Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina.
authors: Nicolás
authors: N
authors: Montalbetti
authors: Qiang
authors: Q
authors: Li
authors: Silvia
authors: S
authors: González-Perrett
authors: Jimena
authors: J
authors: Semprine
authors: Xing-Zhen
authors: XZ
authors: Chen
authors: Horacio F
authors: HF
authors: Cantiello
mesh_terms: D000199:Actins / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology; D005260:Female; D006801:Humans; D008840:Microfilament Proteins / Q000502:physiology; D008954:Models, Biological; D009997:Osmotic Pressure; D016891:Polycystic Kidney, Autosomal Dominant / Q000503:physiopathology; D011247:Pregnancy; D050396:TRPP Cation Channels; D014327:Trophoblasts / Q000187:drug effects / Q000502:physiology*
chemical_list: D000199:Actins; D015638:Cytochalasin D; D008840:Microfilament Proteins; D050396:TRPP Cation Channels