The HUM complex is a myosin-5 adaptor to secretory vesicles

Abstract

The biogenesis of secretory vesicles and their transport to the vesicle supply center (VSC) have been intensively studied in Aspergillus nidulans. The oligomeric complex TRAPPII, which acts as GEF for RAB11 —formerly denoted RabE (Pinar and Peñalva, 2021)— is recruited to trans-Golgi network (TGN) cisternae at late stages of their maturation.TRAPPII recruits RAB11, and when a sufficient amount of the GTPase accumulates on any given TGN cisterna, its identity shifts from ‘Golgi’ to ‘post-Golgi’, engages molecular motors and tears off into secretory vesicles that are swiftly transported to the VSC. F-actin dependent my- osin-5 focuses secretory vesicles at the VSC. Myosin-5 contains a motor domain, a coiled-coil domain mediating dimerization, and a C-terminal globular head domain mediating cargo recognition. Using shotgun proteomics combined with bottom-up reconstitution approaches, we have characterized the HUM complex, consisting of UDS1 (upregulated during septation), HMSV (hook of myosin to secretory vesicles) and the dimeric globular head domain of myosin-5 (Pinar et al., 2022). By interaction of RAB11 with both the GTD and UDS1, the HUM complex acts as adaptor of RAB11 secretory vesicles to the motor. The phenotype of HUM ablation resembles that of a partial deficiency of myosin-5, and SVs do not concentrate in the SPK although they arrive to the apical dome by MT-dependent transport. As expected from the deficient SV focusing resulting from disabling HUM, uds1Δ and hmsVΔ affect hyphal morphogenesis.