Biology subjects

Frisby, D.

Publications and source records attributed to Frisby, D..

2 recordsLinked to original sources

bioRxiv2026

Branched actin constrains endosomal cargo to control sorting and fission

At the early endosome, cargos are sorted into subdomains; receptors destined for recycling to the plasma membrane are sorted into tubulovesicular structures that undergo fission and release cargo-laden vesicles that traffic along microtubules. Although branched actin has been implicated in the establishment/maintenance of endosomal membrane subdomains, its role in cargo segregation, fission, and recycling has not been extensively studied. Using inhibitors of formin-and ARP2/3-mediated actin assembly, we show that branched actin, but not linear actin, is required for endosome fission and receptor recycling. To examine the spatial relationship between actin and cargo, we transfected cells with constitutively active RAB5 Q79L to generate enlarged endosomes and demonstrated that internalized transferrin localized to discrete endosomal regions adjacent to branched actin. ARP2/3 inhibition disrupted this organization, resulting in broader cargo distribution on the endosomal membrane and coalescence of degradative and retrieval subdomains. Consistent with impaired endosomal sorting and fission, branched actin inhibition led to cargo accumulation. Our findings identify ARP2/3-mediated branched actin as a key regulator of cargo segregation, subdomain maintenance, and fission at the early endosome.

cell biology↗

bioRxiv2024

Endosomal actin branching, fission and receptor recycling require FCHSD2 recruitment by MICAL-L1

Endosome fission is required for the release of carrier vesicles and the recycling of receptors to the plasma membrane. Early events in endosome budding and fission rely on actin branching to constrict the endosomal membrane, ultimately leading to nucleotide hydrolysis and enzymatic fission. However, our current understanding of this process is limited, particularly regarding the coordination between the early and late steps of endosomal fission. Here we have identified a novel interaction between the endosomal scaffolding protein, MICAL-L1, and the human homolog of the Drosophila Nervous Wreck (Nwk) protein, FCH and double SH3 domains protein 2 (FCHSD2). We demonstrate that MICAL-L1 recruits FCHSD2 to the endosomal membrane, where it is required for ARP2/3-mediated generation of branched actin, endosome fission and receptor recycling to the plasma membrane. Since MICAL-L1 first recruits FCHSD2 to the endosomal membrane, and is subsequently responsible for recruitment of the ATPase and fission protein EHD1 to endosomes, our findings support a model in which MICAL-L1 orchestrates endosomal fission by connecting between the early actin-driven and subsequent nucleotide hydrolysis steps of the process.

cell biology↗