TY - JOUR
T1 - Bypassing the Greatwall-Endosulfine pathway
T2 - Plasticity of a pivotal cell-cycle regulatory module in Drosophila melanogaster and caenorhabditis elegans
AU - Kim, Min Young
AU - Bucciarelli, Elisabetta
AU - Morton, Diane G.
AU - Williams, Byron C.
AU - Blake-Hodek, Kristina
AU - Pellacani, Claudia
AU - Von Stetina, Jessica R.
AU - Hu, Xiaoqian
AU - Somma, Maria Patrizia
AU - Drummond-Barbosa, Daniela
AU - Goldberg, Michael L.
PY - 2012/8/1
Y1 - 2012/8/1
N2 - In vertebrates, mitotic and meiotic M phase is facilitated by the kinase Greatwall (Gwl), which phosphorylates a conserved sequence in the effector Endosulfine (Endos). Phosphorylated Endos inactivates the phosphatase PP2A/B55 to stabilize M-phasespecific phosphorylations added to many proteins by cyclin-dependent kinases (CDKs). We show here that this module functions essentially identically in Drosophila melanogaster and is necessary for proper mitotic and meiotic cell division in a wide variety of tissues. Despite the importance and evolutionary conservation of this pathway between insects and vertebrates, it can be bypassed in at least two situations. First, heterozygosity for loss-of-function mutations of twins, which encodes the Drosophila B55 protein, suppresses the effects of endos or gwl mutations. Several types of cell division occur normally in twins heterozygotes in the complete absence of Endos or the near absence of Gwl. Second, this module is nonessential in the nematode Caenorhaditis elegans. The worm genome does not contain an obvious ortholog of gwl, although it encodes a single Endos protein with a surprisingly well-conserved Gwl target site. Deletion of this site from worm Endos has no obvious effects on cell divisions involved in viability or reproduction under normal laboratory conditions. In contrast to these situations, removal of one copy of twins does not completely bypass the requirement for endos or gwl for Drosophila female fertility, although reducing twins dosage reverses the meiotic maturation defects of hypomorphic gwl mutants. These results have interesting implications for the function and evolution of the mechanisms modulating removal of CDKdirected phosphorylations.
AB - In vertebrates, mitotic and meiotic M phase is facilitated by the kinase Greatwall (Gwl), which phosphorylates a conserved sequence in the effector Endosulfine (Endos). Phosphorylated Endos inactivates the phosphatase PP2A/B55 to stabilize M-phasespecific phosphorylations added to many proteins by cyclin-dependent kinases (CDKs). We show here that this module functions essentially identically in Drosophila melanogaster and is necessary for proper mitotic and meiotic cell division in a wide variety of tissues. Despite the importance and evolutionary conservation of this pathway between insects and vertebrates, it can be bypassed in at least two situations. First, heterozygosity for loss-of-function mutations of twins, which encodes the Drosophila B55 protein, suppresses the effects of endos or gwl mutations. Several types of cell division occur normally in twins heterozygotes in the complete absence of Endos or the near absence of Gwl. Second, this module is nonessential in the nematode Caenorhaditis elegans. The worm genome does not contain an obvious ortholog of gwl, although it encodes a single Endos protein with a surprisingly well-conserved Gwl target site. Deletion of this site from worm Endos has no obvious effects on cell divisions involved in viability or reproduction under normal laboratory conditions. In contrast to these situations, removal of one copy of twins does not completely bypass the requirement for endos or gwl for Drosophila female fertility, although reducing twins dosage reverses the meiotic maturation defects of hypomorphic gwl mutants. These results have interesting implications for the function and evolution of the mechanisms modulating removal of CDKdirected phosphorylations.
UR - http://www.scopus.com/inward/record.url?scp=84865064000&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84865064000&partnerID=8YFLogxK
U2 - 10.1534/genetics.112.140574
DO - 10.1534/genetics.112.140574
M3 - Article
C2 - 22649080
AN - SCOPUS:84865064000
SN - 0016-6731
VL - 191
SP - 1181
EP - 1197
JO - Genetics
JF - Genetics
IS - 4
ER -