SPAT-1/Bora acts with Polo-like kinase 1 to regulate PAR polarity and cell cycle progression

Abstract

During asymmetric cell division, cell polarity and cell cycle progression are tightly coordinated, yet mechanisms controlling both these events are poorly understood. Here we show that the Bora homologue SPAT-1 regulates both PAR polarity and cell cycle progression in C. elegans embryos. We find that, similarly to mammalian cells, SPAT-1 acts with PLK-1 and not with the mitotic kinase Aurora A (AIR-1), as shown in Drosophila. SPAT-1 binds to PLK-1, and depletion of SPAT-1 or PLK-1 leads to similar cell division defects in early embryos, which differ from the defects caused by depletion of AIR-1. Additionally, SPAT-1 and PLK-1 depletion causes impaired polarity with abnormal length of the anterior and posterior PAR domains, and partial plk-1(RNAi) or spat-1(RNAi), but not air-1(RNAi), can rescue the lethality of a par-2 mutant. SPAT-1 is enriched in posterior cells, and this enrichment depends on PAR polarity and PLK-1. Taken together, our data suggest a model in which SPAT-1 promotes the activity of PLK-1 to regulate both cell polarity and cell cycle timing during asymmetric cell division, providing a link between these two processes

Cdk1 plays matchmaker for the Polo-like kinase and its activator SPAT-1/Bora

“…Phosphorylated (p)Bora accumulates at the G2-M transition and pBora/pSPAT-1 co-precipitate with Plk1/PLK-1, both in human cells 19,27 and in C. elegans embryos, 30 suggesting that the interaction between Bora/SPAT-1 and Plk1/PLK-1 might be regulated by phosphorylation. However, Seki et al showed that the phospho-Bora/Plk1 complex is resistant to lambda phosphatase treatment indicating that Bora phosphorylation is dispensable for the interaction between Bora and Plk1, or at least, not required to maintain this interaction.…”

“…Phenotypic and biochemical analysis revealed that AIR-1 either is not the activating kinase or not the only one. 30,31 Therefore, one possibility is that non-modified SPAT-1 might be able to activate PLK-1, similarly to Bora, but AIR-1 is not the physiological kinase and this prevents the detection of this activation in our in vitro assays. Alternatively SPAT-1 might be more dependent than Bora on Cdk1 phosphorylation to interact with and activate PLK-1.…”

Coordinating cell polarity with cell division in space and time

“…The linker domain, which is phosphorylated by Aurora A, would also provide coordination between cell cycle progression and spindle positioning [59]. In C. elegans embryos, downregulation of the Aurora A homolog, AIR-1, causes cell polarity defects [60,61]. PAR-2, normally found at the posterior of one-cell embryos, is found at both poles in air-1(RNAi) embryos, whereas PAR-6 is found in a central band [60].…”

“…In C. elegans embryos, downregulation of the Aurora A homolog, AIR-1, causes cell polarity defects [60,61]. PAR-2, normally found at the posterior of one-cell embryos, is found at both poles in air-1(RNAi) embryos, whereas PAR-6 is found in a central band [60]. It is not known whether AIR-1 phosphorylates PAR-6 or any other PAR protein in C. elegans.…”

“…However, depletion of plk-1 also results in defects in the localization of PAR proteins in one-cell embryos. Furthermore, depletion of plk-1 can partially rescue the lethality and polarity defects of par-2 temperature-sensitive mutants, suggesting that PLK-1 is either a positive regulator of the anterior PAR proteins or a negative regulator of PAR-2 [60]. Whether PAR proteins themselves are substrates of PLK-1 is unknown.…”