Mauve/LYST limits fusion of lysosome-related organelles and promotes centrosomal recruitment of microtubule nucleating proteins

Summary Lysosome-related organelles (LROs) are endosomal compartments carrying tissue-specific proteins, which become enlarged in Chediak-Higashi syndrome (CHS) due to mutations in LYST. Here, we show that Drosophila Mauve, a counterpart of LYST, suppresses vesicle fusion events with lipid droplets (LDs) during the formation of yolk granules (YGs), the LROs of the syncytial embryo, and opposes Rab5, which promotes fusion. Mauve localizes on YGs and at spindle poles, and it co-immunoprecipitates with the LDs’ component and microtubule-associated protein Minispindles/Ch-TOG. Minispindles levels are increased at the enlarged YGs and diminished around centrosomes in mauve-derived mutant embryos. This leads to decreased microtubule nucleation from centrosomes, a defect that can be rescued by dominant-negative Rab5. Together, this reveals an unanticipated link between endosomal vesicles and centrosomes. These findings establish Mauve/LYST’s role in regulating LRO formation and centrosome behavior, a role that could account for the enlarged LROs and centrosome positioning defects at the immune synapse of CHS patients.
Graphical abstract
Highlights • Drosophila Mauve regulates lysosome-related organelle and lipid droplet fusion • Mauve regulates PCM recruitment and microtubule nucleation from centrosomes • Mauve interacts with Rab5, Msps, and γ-tubulin • Mauve/LYST opposes Rab5, which promotes vesicle fusion affecting PCM recruitment
Lattao et al. investigate the role of Mauve, the Drosophila homolog of the gene LYST, which is mutated in the poorly understood Chediak-Higashi syndrome. They show that Mauve/LYST regulates vesicle fusion and microtubule nucleation at centrosomes, revealing an important connection among vesicles, centrosome homeostasis, and microtubule nucleation.