Re overexpressed, the authors observed slow development and delayed development. Because LATS1/2 are centrosomal proteins in mammalian cells also [223], this pathway may very well be conserved and CDK5RAP2 could serve as a hub for its components in 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 for the Dictyostelium centrosome and PP1 was identified in its centrosomal proteome [52], it is actually unclear irrespective of whether there exists a Nek2, PP1, SvkA, Plk module to regulate centrosome splitting in a related fashion as in mammalian cells (see above). The fact that Sapanisertib Autophagy knockout from the hippo orthologue SvkA interferes only using the abscission procedure in the course of cytokinesis but not with centrosome duplication, argues against it getting an essential component from the hypothetical module [160]. U0126 Data Sheet However, knockout of Dictyostelium NdrC (LATS), which can be not aspect in the Nek2/PP1/Mst2/Plk1 module in mammalian cells, outcomes not only in cytokinesis defects but also in centrosome amplification, supporting a function of hippo elements in Dictyostelium centrosome biogenesis [152].Cells 2021, 10,14 ofTwo further, connected STE20-like kinases, NdrA and SepA, were located also at the Dictyostelium centrosome [147,154]. Each proteins co-purified with isolated centrosomes. NdrA was absent from mitotic centrosomes, and this was independent of your phosphorylation state of its upstream regulator MST3. Surprisingly, knockout of NdrA had no obvious 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 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 can be yet another 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 of your Cdc7 kinase from the septation initiation network (SIN) that drives mitotic exit in S. pombe [224]. SepA’s upstream regulator, the small GTPase Spg1, localized for the centrosome as well. According to the conservation of the SIN pathway proteins and the defects in cleavage furrow formation in SepA knockout cells, it became clear that these proteins are aspect of a conserved mitotic exit pathway but are certainly not involved in centrosome duplication or needed for centrosome integrity. By contrast, in analogy to animal cells, Polo-like kinases (Plks), Aurora kinases, and cyclin-dependent kinases (CDKs) along with Nek2 are fantastic candidates for regulators from the centrosome splitting approach, such as corona disassembly and dissolution with the central core layer. Among the seven CDKs discovered in Dictyostelium discoideum [225] CDK1 is the best candidate, since it is active at the time of centrosome splitting. Polo-like kinases and Aurora kinases are represented in the Dictyostelium genome by only a single member every, Plk and AurK, respectively. No centrosomal substrates are recognized for any on the abovementioned Dictyostelium kinases, even so no less than Plk and AurK have been localized at mitotic centrosomes and centromeres [64,115]. Despite its presence at mitotic spindle poles, a function of.