Abstract 1704 Valosin-containing protein p97 extracts capping protein CP110 from the mother centriole to promote ciliogenesis

Fission at endosomes is required to release cargo-laden carrier vesicles so that they can be recycled back to the plasma membrane.Actin branching plays a crucial role in the early stages of endosome fission by constricting the neck of the budding vesicle and facilitating enzyme-mediated fission.However, our understanding of how the early constriction stage and later enzyme-based stage of endosome fission are coordinated is limited, especially regarding the mechanisms of actin regulation throughout the process.We have identified a novel interaction between the human homolog of the Drosophila Nervous Wreck (Nwk) protein, known as FCH and double SH3 domains protein 2 (FCHSD2), and the endosomal scaffolding protein, MICAL-L1.We have shown that FCHSD2 is recruited to the endosome by MICAL-L1, where it is required to generate ARP2/3-mediated branched actin required for endosome fission and receptor recycling.Furthermore, MICAL-L1 also mediates the subsequent recruitment of the ATPase and fission protein EHD1 to endosomes.These findings support a model in which MICAL-L1 serves as a central coordinator of endosomal fission, linking the early actin-driven membrane remodeling to the later stages of nucleotide hydrolysis and enzymatic fission.