Re overexpressed, the authors observed slow development and delayed development. Considering the fact that LATS1/2 are centrosomal proteins in mammalian cells as well [223], this pathway could be conserved and CDK5RAP2 could serve as a hub for its elements at the centrosome. In neurons, loss of CDK5RAP2 decreased Hippodependent YAP/TAZ signaling, possibly affecting cell proliferation which would clarify CDK5RAP2-dependent microcephaly [222]. Even though SvkA, Nek2 and Plk have all been localized microscopically towards the Dictyostelium centrosome and PP1 was identified in its centrosomal proteome [52], it can be unclear no matter whether there exists a Nek2, PP1, SvkA, Plk module to DFHBI-1T custom synthesis regulate centrosome splitting in a equivalent fashion as in mammalian cells (see above). The fact that knockout on the hippo orthologue SvkA interferes only with all the abscission Dihydrojasmonic acid custom synthesis course of action in the course of cytokinesis but not with centrosome duplication, argues against it getting an vital element from the hypothetical module [160]. But, knockout of Dictyostelium NdrC (LATS), which is not element in the Nek2/PP1/Mst2/Plk1 module in mammalian cells, benefits not just in cytokinesis defects but in addition in centrosome amplification, supporting a function of hippo elements in Dictyostelium centrosome biogenesis [152].Cells 2021, ten,14 ofTwo additional, related STE20-like kinases, NdrA and SepA, had been identified also in the Dictyostelium centrosome [147,154]. Each proteins co-purified with isolated centrosomes. NdrA was absent from mitotic centrosomes, and this was independent of the phosphorylation state of its upstream regulator MST3. Surprisingly, knockout of NdrA had no apparent effects on centrosome integrity or its duplication, but rather it impaired phagocytosis. Given that NdrA interacts together with the Golgi-associated membrane protein EmpC and as a result, is connected with vesicle trafficking, the authors concluded that a centrosomal signal originating from NdrA may well regulate phagocytosis [147]. In addition to the phagocytosis defect of CP55null cells mentioned above (2.two.1.) [56], this can be one more indication that centrosomal proteins are involved in Golgi function and phagocytosis in Dictyostelium. SepA was identified inside a screen for cytokinesis mutants [154] and turned out as an orthologue on the Cdc7 kinase in the septation initiation network (SIN) that drives mitotic exit in S. pombe [224]. SepA’s upstream regulator, the tiny GTPase Spg1, localized towards the centrosome at the same time. According to the conservation in the SIN pathway proteins along with the defects in cleavage furrow formation in SepA knockout cells, it became clear that these proteins are element of a conserved mitotic exit pathway but will not be involved in centrosome duplication or necessary for centrosome integrity. By contrast, in analogy to animal cells, Polo-like kinases (Plks), Aurora kinases, and cyclin-dependent kinases (CDKs) as well as Nek2 are excellent candidates for regulators of the centrosome splitting process, which includes corona disassembly and dissolution in the central core layer. Amongst the seven CDKs identified in Dictyostelium discoideum [225] CDK1 may be the finest candidate, since it is active in the time of centrosome splitting. Polo-like kinases and Aurora kinases are represented within the Dictyostelium genome by only 1 member every, Plk and AurK, respectively. No centrosomal substrates are identified for any of the abovementioned Dictyostelium kinases, nevertheless no less than Plk and AurK have been localized at mitotic centrosomes and centromeres [64,115]. In spite of its presence at mitotic spindle poles, a role of.