Calmodulin controls organization of the actin cytoskeleton via regulation of phosphatidylinositol (4,5)-bisphosphate synthesis in Saccharomyces cerevisiae.
Phosphoinositides regulate a wide range of cellular processes, including proliferation, survival, cytoskeleton remodelling and membrane trafficking, yet the mechanisms controlling the kinases, phosphatases and lipases that modulate phosphoinositide levels are poorly understood. In the present study, we describe a mechanism controlling MSS4, the sole phosphatidylinositol (4)-phosphate 5-kinase in Saccharomyces cerevisiae. Mutations in MSS4 and CMD1, encoding the small Ca(2+)-binding protein calmodulin, confer similar phenotypes, including loss of viability and defects in endocytosis and in organization of the actin cytoskeleton. Overexpression of MSS4 suppresses the growth and actin defects of cmd1-226, a temperature-sensitive calmodulin mutant which is defective in the organization of the actin cytoskeleton. Finally, the cmd1-226 mutant exhibits reduced levels of phosphatidylinositol (4,5)-bisphosphate. These findings suggest that calmodulin positively controls MSS4 activity and thereby the actin cytoskeleton.
Desrivières
Sylvane
S
Division of Biochemistry, Biozentrum, University of Basel, Klingelbergstrasse 70, Switzerland.
Cooke
Frank T
FT
Morales-Johansson
Helena
H
Parker
Peter J
PJ
Hall
Michael N
MN
D000199:Actins / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D004705:Endocytosis; D020935:MAP Kinase Signaling System; D009154:Mutation; D010641:Phenotype; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D010770:Phosphotransferases; D017853:Phosphotransferases (Alcohol Group Acceptor); D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D013696:Temperature; D013997:Time Factors
D000199:Actins; D002147:Calmodulin; D019269:Phosphatidylinositol 4,5-Diphosphate; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; D010770:Phosphotransferases; D017853:Phosphotransferases (Alcohol Group Acceptor); C489795:MSS4 protein, S cerevisiae; D011493:Protein Kinase C; D002118:Calcium