Distinct D-Box Motifs in SPD-2 Mediate APC/CFZR-1 -Dependent Degradation and Centrosomal Localization in Caenorhabditis elegans
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Centrosome duplication must be tightly controlled to maintain genomic stability. In Caenorhabditis elegans, the APC/C and co-activator FZR-1 function as negative regulators of centrosome duplication by targeting specific substrates for proteolytic degradation. While C. elegans SAS-5 and ZYG-1 have been identified as substrates of APC/CFZR-1, the mechanism by which APC/CFZR-1-dependent degradation influences centrosome assembly remains elusive. Here, we identified SPD-2, the conserved homolog of human CEP192, as a direct substrate of APC/CFZR-1. We show that loss of APC/CFZR-1 increases SPD-2 levels both in the cytoplasm and at centrosomes, and that SPD-2 physically associates with FZR-1 in vivo. Functional analyses of canonical D-box motifs demonstrate that all three D-box1, 2, and 3 motifs contribute to SPD-2 degradation, but their functions are distinct. Mutating D-box3 alone rescued zyg-1 mutant phenotypes by restoring centrosome duplication and embryonic viability through increased centrosomal SPD-2 and ZYG-1. In contrast, mutation of D-box1 or 2 elevated cellular SPD-2 but did not rescue zyg-1, with D-box1 mutation further reducing centrosomal SPD-2 and exacerbating duplication defects and lethality in zyg-1 mutants. Our results reveal a conserved mechanism for APC/CFZR-1-dependent degradation of SPD-2 and show that its degron motifs have dual functions in degradation and centrosomal localization, ensuring robust control of centrosome assembly during C. elegans embryogenesis.