The calcineurin inhibitor gossypol impairs growth, cell signalling and development in Dictyostelium discoideum.
The Dictyostelium genome harbors single copy genes for both the catalytic and regulatory subunits of the Ca2+/calmodulin-dependent protein phosphatase calcineurin. Since molecular genetic approaches to reduce the expression of these genes have failed so far, we attempted to pharmacologically target calcineurin activity in vivo by using the recently described calcineurin inhibitor, gossypol. Up-regulation of expression of the gene for the Ca2+-ATPase PAT1 in conditions of Ca2+ stress was reduced by gossypol. Dictyostelium wild-type cells treated with 12.5-100 microM gossypol showed reduced growth rates and impaired development. In addition, cell signalling was affected. A cell line that overproduces the catalytic subunit of calcineurin was more resistant to gossypol.
Weissenmayer
Barbara
B
Institut für Biologie - Mikrobiologie, Fachbereich Biologie, Chemie, Pharmazie, Freie Universität Berlin, Königin-Luise-Strasse 12-16, 14195 Berlin, Germany. bweiss@zedat.fu-berlin.de
Boeckeler
Katrina
K
Lahrz
Angela
A
Mutzel
Rupert
R
D000818:Animals; D065095:Calcineurin Inhibitors; D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004023:Dictyostelium / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006072:Gossypol / Q000494:pharmacology*; D008027:Light; D012542:Scattering, Radiation; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation
D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D000242:Cyclic AMP; D000252:Calcium-Transporting ATPases; D006072:Gossypol