The branched actin cytoskeleton is implicated in cellular trafficking. The actin regulator Arp2/3 is activated by the Wiskott-Aldrich syndrome protein homologue (WASH) complex, which is needed for the integrity of endosomes and lysosomes, and for the trafficking from endosomes to subcellular locations. In the amoeba Dictyostelium, loss of WASH disrupts the maturation of lysosomes and blocks exocytosis. In this issue (p. 1785), Robert Insall and colleagues screen for mutants defective in exocytosis. WASH mutants are unable to expel dextran after ingesting it, so new mutants were selected on the basis of excessive retention of fluorescent dextran. The authors identify the maestro HEAT-like repeat-containing protein family member 1 (Mroh1), which localises to lysosomes in both Dictyostelium and mammalian cells. The authors find that, in amoebas, Mroh1 accumulates on maturing lysosomes and is removed together with WASH before post-lysosomes are exocytosed. Mutation of WASH or inhibition of actin polymerisation causes relocalisation of Mroh1 from the cytoplasm to small vesicles. Importantly, loss of Mroh1 does not affect the formation of endosomes but leads to inefficient recycling of WASH and a substantial delay in exocytosis. Taken together, these experiments identify Mroh1 as a cellular partner for the WASH complex at lysosomes with an actin-regulated function in late vesicular sorting.
