Abstract
ABSTRACTCentriole assembly requires a small number of conserved proteins. The precise pathway of centriole assembly has been difficult to study, as the lack of any one of the core assembly proteins [Plk4, Ana2 (the homologue of mammalian STIL), Sas-6, Sas-4 (mammalian CPAP) or Asl (mammalian Cep152)] leads to the absence of centrioles. Here, we use Sas-6 and Ana2 particles (SAPs) as a new model to probe the pathway of centriole and centrosome assembly. SAPs form in Drosophila eggs or embryos when Sas-6 and Ana2 are overexpressed. SAP assembly requires Sas-4, but not Plk4, whereas Asl helps to initiate SAP assembly but is not required for SAP growth. Although not centrioles, SAPs recruit and organise many centriole and centrosome components, nucleate microtubules, organise actin structures and compete with endogenous centrosomes to form mitotic spindle poles. SAPs require Asl to efficiently recruit pericentriolar material (PCM), but Spd-2 (the homologue of mammalian Cep192) can promote some PCM assembly independently of Asl. These observations provide new insights into the pathways of centriole and centrosome assembly.
Highlights
Centrioles are small cylindrical structures that form centrosomes and cilia, organelles that play an important part in many aspects of cell organisation and whose dysfunction has been linked to a plethora of human pathologies (Bettencourt-Dias et al, 2011; Nigg and Holland, 2018; Nigg and Raff, 2009)
We show here that the core Drosophila centriole cartwheel proteins (Sas-6, Ana2 and Sas-4) have a remarkable ability to self-organise into macromolecular structures (SAPs)
Spindle assembly abnormal protein 6 (Sas-6) and Ana2 particles (SAPs) assembly is dependent on Sas-4. This appears to be different to the situation for centriole assembly in C. elegans embryos where SAS-6 and SAS-5 can first form a central tube that recruits SAS-4
Summary
Centrioles are small cylindrical structures that form centrosomes and cilia, organelles that play an important part in many aspects of cell organisation and whose dysfunction has been linked to a plethora of human pathologies (Bettencourt-Dias et al, 2011; Nigg and Holland, 2018; Nigg and Raff, 2009). Hundreds of proteins are concentrated at centrioles and centrosomes (Alves-Cruzeiro et al, 2014), only a surprisingly small number of these proteins are essential for centriole and mitotic centrosome assembly (Banterle and Gönczy, 2017; Conduit et al, 2015a; Gönczy and Hatzopoulos, 2019; Nigg and Holland, 2018) (Fig. 1A). Classical genetic and large scale RNAi screens in Caenorhabditis elegans identified a small set of genes that are essential for centriole and mitotic centrosome assembly in the early worm embryo (Schwarz et al, 2018). Studies in other systems revealed that functional homologues of the C. elegans proteins are involved in centriole assembly (Banterle and Gönczy, 2017; Breslow and Holland, 2019; Conduit et al, 2015a; Nigg and Holland, 2018), but it has been much harder to precisely order these proteins into functional pathways, largely because the absence of a key centriole assembly protein leads to the absence of centrioles, and so epistatic relationships cannot be inferred
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