Re overexpressed, the authors observed slow growth and delayed development. Given that LATS1/2 are centrosomal

Re overexpressed, the authors observed slow growth and delayed development. Given that LATS1/2 are centrosomal proteins in mammalian cells too [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 explain CDK5RAP2-dependent microcephaly [222]. Even though SvkA, Nek2 and Plk have all been localized microscopically for the Dictyostelium Cetylpyridinium medchemexpress centrosome and PP1 was identified in its centrosomal proteome [52], it is actually unclear no matter if there exists a Nek2, PP1, SvkA, Plk module to regulate centrosome splitting in a similar fashion as in mammalian cells (see above). The fact that knockout from the hippo orthologue SvkA interferes only together with the abscission course of action through cytokinesis but not with centrosome duplication, argues against it becoming an essential element of the hypothetical module [160]. Yet, knockout of Dictyostelium NdrC (LATS), which is not part on the Nek2/PP1/Mst2/Plk1 module in mammalian cells, results not GW-870086 supplier merely in cytokinesis defects but additionally in centrosome amplification, supporting a role of hippo components in Dictyostelium centrosome biogenesis [152].Cells 2021, 10,14 ofTwo further, related STE20-like kinases, NdrA and SepA, had been identified also at the Dictyostelium centrosome [147,154]. Both 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 clear effects on centrosome integrity or its duplication, but rather it impaired phagocytosis. Because NdrA interacts with all the Golgi-associated membrane protein EmpC and as a result, is associated with vesicle trafficking, the authors concluded that a centrosomal signal originating from NdrA may perhaps regulate phagocytosis [147]. In addition to the phagocytosis defect of CP55null cells described above (2.two.1.) [56], this really is an additional indication that centrosomal proteins are involved in Golgi function and phagocytosis in Dictyostelium. SepA was identified in a screen for cytokinesis mutants [154] and turned out as an orthologue in the Cdc7 kinase in the septation initiation network (SIN) that drives mitotic exit in S. pombe [224]. SepA’s upstream regulator, the compact GTPase Spg1, localized to the centrosome too. Determined by the conservation with the SIN pathway proteins and the defects in cleavage furrow formation in SepA knockout cells, it became clear that these proteins are part of a conserved mitotic exit pathway but usually are not involved in centrosome duplication or essential 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 superior candidates for regulators of the centrosome splitting process, which includes corona disassembly and dissolution of your central core layer. Among the seven CDKs identified in Dictyostelium discoideum [225] CDK1 is the most effective candidate, since it is active at the time of centrosome splitting. Polo-like kinases and Aurora kinases are represented within the Dictyostelium genome by only a single member every, Plk and AurK, respectively. No centrosomal substrates are recognized for any from the abovementioned Dictyostelium kinases, nevertheless a minimum of Plk and AurK have already been localized at mitotic centrosomes and centromeres [64,115]. Despite its presence at mitotic spindle poles, a role of.