Bypassing the Greatwall-Endosulfine pathway: plasticity of a pivotal cell-cycle regulatory module in Drosophila melanogaster and Caenorhabditis elegans.
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-phase-specific 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 CDK-directed phosphorylations.
Department of Biochemistry and Molecular Biology, Division of Reproductive Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA.
Min-Young
MY
Kim
Elisabetta
E
Bucciarelli
Diane G
DG
Morton
Byron C
BC
Williams
Kristina
K
Blake-Hodek
Claudia
C
Pellacani
Jessica R
JR
Von Stetina
Xiaoqian
X
Hu
Maria Patrizia
MP
Somma
Daniela
D
Drummond-Barbosa
Michael L
ML
Goldberg
D000483:Alleles; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D023061:Gene Order; D006579:Heterozygote; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008540:Meiosis; D008938:Mitosis; D009154:Mutation; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction
D029721:Drosophila Proteins; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D021122:Protein Subunits; C075663:endosulfine; C490167:Gwl protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D002265:Carboxylic Ester Hydrolases; C119357:protein phosphatase methylesterase-1; D010749:Phosphoprotein Phosphatases