Altered distribution and co-localization of polycystin-2 with polycystin-1 in MDCK cells after wounding stress

作者：Scheffers MS; van der Bent P; van de Wal A; van Eendenburg J; Breuning MH; de Heer E; Peters DJM^*

来源：Experimental Cell Research, 2004, 292(1): 219-230.

DOI：10.1016/j.yexcr.2003.08.019

• ADPKD
• polycystin-1
• polycystin-2
• co-localization
• MDCK
• wound healing

Polycystin-1 and -2 are integral membrane glycoproteins defective in autosomal dominant polycystic kidney disease (ADPKD). Recent studies showed a coupled polycystin-land -2 action in cell signaling and channel activation suggesting an important biological role for the two proteins at the plasma membrane. To gain a better understanding about the (co)-distribution and dynamics of the polycystin-1 and -2 complex under stress conditions, we used a wound-healing model of Madine Darby canine kidney (MDCK) renal epithelial cells. In this model, cells near the wound edge undergo a process of reorganization to active migration, while cells further from the edge are unaffected and remain confluent. For the first time, endogenous polycystin-1 and -2 were found to partly co-localize in the plasma membrane of confluent monolayers, and both proteins co-localized in the primary cilium. Upon wound healing, the association of polycystin-2 to the membrane was greatly reduced at the wound edge and the submarginal cells. Polycystin-1 remained incorporated to the membrane at the edge of the cell sheet at all time points, although strongly reduced in lamellipodia-forming cells. Adherens junctions and desmosomes, and respective connected actin and keratin cytoskeleton were also disturbed in lamellipodia-forming cells. We propose that altered subcellular localization of polycystin-1 and -2 as a result of stress will affect signaling and other cellular processes mediated by these proteins.

• 出版日期2004-1-1