Mutation of Ser172 in yeast β tubulin induces defects in microtubule dynamics and cell division.
Ser172 of β tubulin is an important residue that is mutated in a human brain disease and phosphorylated by the cyclin-dependent kinase Cdk1 in mammalian cells. To examine the role of this residue, we used the yeast S. cerevisiae as a model and produced two different mutations (S172A and S172E) of the conserved Ser172 in the yeast β tubulin Tub2p. The two mutants showed impaired cell growth on benomyl-containing medium and at cold temperatures, altered microtubule (MT) dynamics, and altered nucleus positioning and segregation. When cytoplasmic MT effectors Dyn1p or Kar9p were deleted in S172A and S172E mutants, cells were viable but presented increased ploidy. Furthermore, the two β tubulin mutations exhibited synthetic lethal interactions with Bik1p, Bim1p or Kar3p, which are effectors of cytoplasmic and spindle MTs. In the absence of Mad2p-dependent spindle checkpoint, both mutations are deleterious. These findings show the importance of Ser172 for the correct function of both cytoplasmic and spindle MTs and for normal cell division.
Institute of Biochemistry, ETH Zurich, Zurich, Switzerland.
Fabrice
F
Caudron
Eric
E
Denarier
Jenny-Constanza
JC
Thibout-Quintana
Jacques
J
Brocard
Annie
A
Andrieux
Anne
A
Fourest-Lieuvin
D000595:Amino Acid Sequence; D002453:Cell Cycle; D002455:Cell Division; D008870:Microtubules; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000235:genetics*; D014404:Tubulin / Q000737:chemistry / Q000235:genetics*
D014404:Tubulin; D012694:Serine