Cyclic-AMP deficient MDCK cells form tubules.
It has been known for many years that MDCK cells form blister-like structures, termed domes. During an examination of the morphology of a large number of MDCK clones, we found that two stable morphotypes exist in an MDCK cell population-namely, dome-forming and tubule-forming clones. When maintained at high cell density, tubule-forming clones displayed large numbers of anastomosing tubules which contained lumens. The frequency of observation of the tubule-forming clones in an MDCK population was 0.7%. Tubule-forming MDCK clones should be useful in studying tubule morphogenesis. While agents that affect protein kinase A activity increased dome formation, the same agents abolished the formation of tubules in all tubule-forming clones. In contrast, drugs that stimulate protein kinase C activity (phorbol esters and staurosporine) decreased dome formation an increased tubule morphogenesis in all MDCK morphotypes. Tubule-forming clones were found to have lower resting levels of cyclic-AMP and to respond to forskolin stimulation of adenylate cyclase less readily. Hence, signals transmitted by the protein kinase C pathway appear to lead to tubule formation in MDCK cells, while signals transmitted through the protein kinase A pathway lead to dome formation.
Klebe
R J
RJ
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284, USA.
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Ghosh
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D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002999:Clone Cells; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000172:deficiency*; D004285:Dogs; D007621:Karyotyping; D007684:Kidney Tubules / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D008954:Models, Biological; D009024:Morphogenesis / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000643:Ammonium Chloride; D005576:Colforsin; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate