CCDC41 Drives Oocyte Meiotic Progression by Promoting Rab11a/Rab7‐Positive Vesicle Fusion with Target Membranes

Coiled-coil domain-containing protein 41 (CCDC41), a core component of centriolar distal appendages involved in centriole assembly and ciliary vesicle docking, has remained functionally uncharacterized in oocyte meiosis. Here, it is demonstrated that CCDC41 is a versatile player in three key steps of oocyte meiosis. First, CCDC41 depletion significantly impaired meiotic resumption, a defect mechanistically linked to reduced Cyclin B1 accumulation, compromised cyclin-dependent kinase 1 (CDK1) activation, and dysregulation of the anaphase-promoting complex/cyclosome (APC/C) co-activators Cdc20 homolog 1 (CDH1) and cell division cycle 20 (CDC20). Notably, this arrest is rescued by pharmacological inhibition of CDC20. Second, CCDC41 knockdown disrupted spindle cortical migration, a defect ascribed to impaired fusion of RAS oncogene family (Rab11a)-positive vesicles with the plasma membrane, which in turn prevented the anchoring of cytoplasmic F-actin to the cortex. Third, CCDC41 depletion accelerated anaphase onset by prematurely silencing the spindle assembly checkpoint and enhancing CDC20-mediated Cyclin B1 degradation. Mechanistically, CCDC41 localizes to lysosomes, and its loss delays RAS oncogene family member 7 (Rab7)-positive late endosome fusion with these organelles, causing cytoplasmic dispersion of active cathepsin. Critically, pharmacological or genetic inhibition of cathepsin B restored meiotic progression in CCDC41-deficient oocytes. Collectively, the findings establish that CCDC41 is essential for faithful meiotic completion, it regulates CDC20 activity through promoting cathepsin delivery to lysosomes, and ensures proper spindle migration via Rab11a-dependent F-actin anchoring.