Endosomal actin attenuation and fission are regulated by MICAL2

Endosome fission is essential for the generation of carrier vesicles and recycling of receptors to the plasma membrane. Early events in endosome fission depend on the generation of Arp2/3-mediated branched actin, which segregates cargo and constricts the endosomal membrane to form buds. It has been proposed that once membrane buds have been formed, branched actin attenuation is necessary for fission proteins, such as EHD1, to access the endosomal neck and complete the cleavage process. Whereas several proteins and complexes involved in actin growth at endosomes have been characterized, less is known about actin attenuation at endosomes. In our study, we identified MICAL2, a constitutively active actin-regulatory monooxygenase, as a key regulator of endosomal fission, likely through its regulation of branched actin. MICAL2 depletion, or inhibition of its monooxygenase activity, resulted in a substantial increase in branched actin associated with endosomes. Moreover, we demonstrate that MICAL2 is required for both endosome fission and the recycling of clathrin-dependent cargo. Overall, our study highlights a novel role for MICAL2 in regulating actin at endosomes, thereby facilitating fission and recycling.