Alström syndrome proteins are novel regulators of centriolar cartwheel assembly and centrosome homeostasis inDrosophila

Abstract Centrioles play central functions in cell division and differentiation. Alterations of centriole number or function lead to various diseases including cancer or microcephaly. Centriole duplication is a highly conserved mechanism among eukaryotes during which Ana2/STIL phosphorylation by Plk4 allows the recruitment of the cartwheel protein Sas-6 to initiate procentriole assembly. Here we show that the two Drosophila Alms1 proteins (Alms1a and Alms1b), orthologs of the human ALMS1 protein associated with the Alström syndrome, are novel regulators of the assembly of the pro-centriole cartwheel and pericentriolar material (PCM). Using Ultrastructure Expansion Microscopy we show that Alms1a is a PCM protein loaded at the proximal end of centrioles at the onset of their assembly in several fly tissues, while Alms1b caps the proximal end of only maturating centrioles. We demonstrate that chronic loss of Alms1 proteins affects PCM maturation, whereas their acute loss impairs the onset of procentriole formation by reducing Ana2 amplification leading to complete failure of Sas-6 recruitment. Our work identifies Alms1 proteins as novel centriolar components that finely tune centrosome homeostasis and the initiation of cartwheel formation in Drosophila . It also reveals strong buffering capacity of tissues in response to perturbations of the centriole assembly process.