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This Article Full Text Full Text (PDF) All Versions of this Article: 579/3/717    most recent jphysiol.2006.125583v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Montalbetti, N. Articles by Cantiello, H. F. Search for Related Content PubMed PubMed Citation Articles by Montalbetti, N. Articles by Cantiello, H. F. Related Collections Cellular

¹ Laboratorio de Canales Iónicos, Departamento de Fisicoquímica y Química Analítica, Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina
² Department of Physiology, University of Alberta, Edmonton, Canada
³ Renal Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA

Polycystin-2 (PC2), encoded by PKD2, which is one of the genes whose mutations cause polycystic kidney disease, is abundantly produced in the apical domain of the syncytiotrophoblast (hST) of term human placenta. PC2, a TRP-type (TRPP2) non-selective cation channel, is present in primary cilia of renal epithelial cells, a microtubule-based ancillary structure with sensory function. The hST has abundant cytoskeletal structures, and actin filament dynamics regulate PC2 channel function in this epithelium. However, it is expected that the apical hST excludes microtubular structures. Here, we demonstrated by Western blot and immunocytochemical analyses that hST apical vesicles indeed contain microtubule structural components, including tubulin isoforms, acetylated -tubulin, and the kinesin motor proteins KIF3A and KIF3B. PC2 and tubulin were substantially colocalized in hST vesicles. Treatment of hST vesicles with either the microtubular disrupter colchicine (15 µM) or the microtubular stabilizer paclitaxel (taxol, 15 µM) resulted in distinct patterns of microtubular re-organization and PC2 redistribution. We also observed that changes in microtubular dynamics regulate PC2 channel function. Addition of colchicine rapidly inhibited PC2 channel activity in lipid-bilayer reconstituted hST membranes. Addition of either tubulin and GTP, or taxol, however, stimulated PC2 channel activity in control hST membranes. Interestingly, we found that the kinesin motor protein KIF3A was capable of increasing PC2 channel activity in hST. We believe that the data are the first to provide a direct demonstration of a microtubular interaction with PC2 in the hST. This interaction thus plays an important regulatory role in the control of ion transport in the human placenta.

(Received 26 November 2006; accepted after revision 18 December 2006; first published online 4 January 2007)
Corresponding author H. F. Cantiello: Renal Unit, Massachusetts General Hospital East, Building 149, 13th Street, Charlestown, MA 02129, USA. Email: cantiello{at}helix.mgh.harvard.edu

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