Involvement of the membrane-cytoskeleton in development of epithelial cell polarity.
The generation of cell surface polarity in transporting epithelial cells occurs in three distinct stages that involve cell-cell recognition and adhesion, cell surface remodelling to form biochemically and functionally distinct cell surface domains, and development of vectorial function. A widely used model system to study mechanisms involved in these stages is the Madin-Darby canine kidney (MDCK) cell line. Under appropriate growth conditions, MDCK cells develop in similar stages into polarized, multicellular epithelial structures. Analysis of membrane-cytoskeletal proteins ankyrin and fodrin during development of MDCK cell surface polarity shows that they gradually assemble into an insoluble protein complex on the basal-lateral membrane domain upon cell-cell adhesion, concomitantly with the redistribution of Na+,K(+)-ATPase, a marker protein of the basal-lateral membrane. Biochemical analysis shows that ankyrin, fodrin occur in a complex with Na+,K(+)-ATPase and the cell adhesion molecule uvomorulin in MDCK cells. A model is presented in which assembly of membrane-cytoskeletal complexes at sites of uvomorulin-induced cell-cell contact causes a remodelling of the cell surface distribution of specific membrane proteins which, in turn, contributes to the generation of epithelial cell surface polarity.
Nelson
W J
WJ
Institute for Cancer Research, Philadelphia, PA 19111.
Hammerton
R W
RW
Wang
A Z
AZ
Shore
E M
EM
D000818:Animals; D017487:Ankyrins; D001798:Blood Proteins / Q000502:physiology; D015820:Cadherins / Q000378:metabolism; D002352:Carrier Proteins / Q000502:physiology; D002448:Cell Adhesion; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000502:physiology* / Q000648:ultrastructure; D003598:Cytoskeletal Proteins / Q000502:physiology; D003599:Cytoskeleton / Q000502:physiology* / Q000648:ultrastructure; D004847:Epithelial Cells; D004848:Epithelium / Q000502:physiology / Q000648:ultrastructure; D008565:Membrane Proteins / Q000502:physiology; D008840:Microfilament Proteins / Q000502:physiology; D008954:Models, Biological; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013997:Time Factors; D013049:Spectrin
D017487:Ankyrins; D001798:Blood Proteins; D015820:Cadherins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D000254:Sodium-Potassium-Exchanging ATPase; D013049:Spectrin