Drosophila Alms1 proteins regulate centriolar cartwheel assembly by enabling Plk4-Ana2 amplification loop.

Centrioles play a central role in cell division by recruiting pericentriolar material (PCM) to form the centrosome. Alterations in centriole number or function lead to various diseases including cancer or microcephaly. Centriole duplication is a highly conserved mechanism in eukaryotes. Here, we show that the two Drosophila orthologs of the Alström syndrome protein 1 (Alms1a and Alms1b) are unexpected novel players of centriole duplication in fly. Using Ultrastructure Expansion Microscopy, we reveal that Alms1a is a PCM protein that is loaded proximally on centrioles at the onset of procentriole formation, whereas Alms1b caps the base of mature centrioles. We demonstrate that chronic loss of Alms1 proteins (with RNA null alleles) affects PCM maturation, whereas their acute loss (in RNAi KD) completely disrupts procentriole formation before Sas-6 cartwheel assembly. We establish that Alms1 proteins are required for the amplification of the Plk4-Ana2 pool at the duplication site and the subsequent Sas-6 recruitment. Thus, Alms1 proteins are novel critical but highly buffered regulators of PCM and cartwheel assembly in flies.