DYRK kinase Pom1 drives F-BAR protein Cdc15 from the membrane to promote medial division

Abstract

Phosphorylation by the DYRK kinase Pom1 is one of two major signals for proper division site placement in Schizosaccharomyces pombe. Pom1 phosphorylation of F-BAR protein Cdc15 inhibits its membrane and protein binding, thus inhibiting scaffolding of the cytokinetic ring and preventing mislocalized division.

Fission yeast Pak1 phosphorylates anillin-like Mid1 for spatial control of cytokinesis

“…The full role of Pak1 in cytokinesis likely involves proteins beyond Mid1, consistent with our identification of Cdc15, Cyk3, and Rng10 as new substrates for Pak1. We note that Cdc15 and Cyk3 are also phosphorylated by the cell polarity kinases Pom1 and Kin1 ( Kettenbach et al, 2015 ; Lee et al, 2018 ; Bhattacharjee et al, 2020 ), and Pom1 further phosphorylates the Rng10 ligand Rga7 ( Kettenbach et al, 2015 ). Put together, these connections reveal a strong and growing role for cell polarity signaling in the regulation of CAR proteins for cytokinesis.…”

“…We focused on the new Pak1 substrates Cdc15 and Mid1 due to their roles in cytokinesis. Cdc15 is a membrane-binding phosphoprotein that connects multiple cytokinesis factors to the CAR ( Roberts-Galbraith et al, 2010 ; Martín-García et al, 2014 ; Kettenbach et al, 2015 ; Ren et al, 2015 ; Willet et al, 2015 ; Lee et al, 2018 , Bhattacharjee et al, 2020 ) and exhibits synthetic genetic defects with pak1 mutations ( Fig. 4, A and B ).…”

“…Recent studies identified a direct role for the cell polarity kinases Pom1 and Kin1 in fission yeast cytokinesis. Kin1 and Pom1 phosphorylate multiple cytokinesis proteins including shared substrates ( Kettenbach et al, 2015 ; Lee et al, 2018 ; Bhattacharjee et al, 2020 ). Both in vitro and in cells, Kin1 and Pom1 phosphorylated largely nonoverlapping residues on these shared substrates ( Lee et al, 2018 ).…”

Time-varying mobility and turnover of actomyosin ring components during cytokinesis inSchizosaccharomyces pombe

“…Cdc15 is a crucial structural scaffold protein and is known to be cell cycle regulated (Fankhauser et al, 1995;Swaffer et al, 2018). It was previously indicated that Cdc15 localization and function during the early stages of AMR assembly might be regulated through de-/ phosphorylation of its unstructured region and SH3 domain by the septation initiation network (SIN) and Pom1, respectively (Figure 3A; (Fankhauser et al, 1995;Wachtler et al, 2006;Roberts-Galbraith et al, 2010;Mcdonald et al, 2015;Bhattacharjee et al, 2020). However, the exact function of the posttranslational modification dependent regulation of Cdc15 structure during cytokinesis is not fully understood yet.…”

“…Additionally, we included the truncated version of Cdc15 lacking its SH3 domain in our experiment (Roberts-Galbraith et al, 2009). The Cdc15 SH3 domain is known to recruit proline-rich (PxxP) motifcontaining proteins (such as Pxl1 and Fic1) to the AMR (Roberts-Galbraith et al, 2009;Ren et al, 2015;Bhattacharjee et al, 2020) and thus is expected to play an important role in the formation of the AMR.…”