Altered distribution and co-localization of polycystin-2 with polycystin-1 in MDCK cells after wounding stress.
Polycystin-1 and -2 are integral membrane glycoproteins defective in autosomal dominant polycystic kidney disease (ADPKD). Recent studies showed a coupled polycystin-1 and -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.
Scheffers
Martijn S
MS
Department of Human Genetics, Leiden University Medical Center, 2333 AL Leiden, The Netherlands.
van der Bent
Paola
P
van de Wal
Annemieke
A
van Eendenburg
Jaap
J
Breuning
Martijn H
MH
de Heer
Emile
E
Peters
Dorien J M
DJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002923:Cilia / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D003896:Desmosomes / Q000378:metabolism; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism*; D007668:Kidney / Q000166:cytology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D050396:TRPP Cation Channels; D013997:Time Factors; D014018:Tissue Distribution; D014945:Wound Healing / Q000276:immunology*
D000911:Antibodies, Monoclonal; D008565:Membrane Proteins; D011506:Proteins; D050396:TRPP Cation Channels