Abstract
Polo-like kinases (Plks) are a family of conserved regulators of a variety of events throughout the cell cycle, expanded from one Plk in yeast to five Plks in mammals (Plk1-5). Plk1 is the best characterized member of the Plk family, homolog to the founding member Polo of Drosophila, and plays a major role in cell cycle progression by triggering G2/M transition. Plk4/Sak (for Snk (Serum-inducible kinase) akin kinase) is a unique member of the family, structurally distinct from other Plk members, with essential functions in centriole duplication. The genome of the trematode parasite Schistosoma mansoni contains only two Plk genes encoding SmPlk1 and SmSak. SmPlk1 has been shown already to be required for gametogenesis and parasite reproduction. In this work, in situ hybridization indicated that the structurally conserved Plk4 protein, SmSak, was largely expressed in schistosome female ovary and vitellarium. Expression of SmSak in Xenopus oocytes confirmed its Plk4 conserved function in centriole amplification. Moreover, analysis of the function of SmSak in meiosis progression of G2-blocked Xenopus oocytes indicated that, in contrast to SmPlk1, SmSak cannot induce G2/M transition in the absence of endogenous Plk1 (Plx1). Unexpectedly, meiosis progression was spontaneously observed in Plx1-depleted oocytes co-expressing SmSak and SmPlk1. Molecular interaction between SmSak and SmPlk1 was confirmed by co-immunoprecipitation of both proteins. These data indicate that Plk1 and Plk4 proteins have the potential to interact and cross-activate in cells, thus attributing for the first time a potential role of Plk4 proteins in meiosis/mitosis entry. This unexpected role of SmSak in meiosis could be relevant to further consider the function of this novel Plk in schistosome reproduction.
Highlights
Polo-like kinases (Plks) are important regulators of the cell cycle progression during M-phase, primarily involved in the assembly and dynamics of the mitotic spindle apparatus and in the regulation of the activation of cyclin-dependent protein kinases (Cdks) [1,2]
We have previously shown that the expression of native SmSak (Figure 4 A, D) or SmPlk1 ([23], Figure 4D) in immature Xenopus oocytes was not sufficient to release their arrest in late G2 of meiosis I, but that these oocytes were capable of responding to a PG stimulus and to undergo germinal vesicle breakdown (GVBD), exactly as control oocytes
The severity of schistosomiasis is primarily due to the fecundity of the worms which develop in human hosts
Summary
Polo-like kinases (Plks) are important regulators of the cell cycle progression during M-phase, primarily involved in the assembly and dynamics of the mitotic spindle apparatus and in the regulation of the activation of cyclin-dependent protein kinases (Cdks) [1,2]. Metazoans possess multiple Plks which have different functions but a common structure composed of a conserved amino-terminal S/T kinase domain and a carboxy-terminal Polo-box domain (PBD) responsible for protein-protein interactions and subcellular localization [3]. Plk have similar structures with two conserved polo boxes that can dimerise intramolecularly and form a pocket for binding to phospho S/T residues (inside of the S-pS/pT-P-X sequence) inducing conformational changes and kinase activation [5,6]. The roles of Plk ( named Snk for Serum inducible kinase) and Plk (Fnk for FGF-inducible kinase) are not completely understood [4]
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