Characterising the role of Dmon1 in endosomal trafficking

Endosomal trafficking regulates the cellular transport of extracellular cargo from the plasma membrane to the lysosome through endocytic vesicles that mature along the way. Rab conversion, the replacement of the small GTPase Rab5 on endosomes with Rab7, is an important step in their maturation. Previous studies in other systems have shown that members of the Mon1 protein family are important for Rab7 recruitment, although the underlying mechanisms remain unclear. On page 1583, Thomas Klein and co-workers now characterise the Drosophila Mon1 homologue Dmon1 (encoded by CG11926). They find that loss of Dmon1 results in enlarged maturing endosomes that lack Rab7 and contain Notch and other transmembrane proteins as their cargo. The authors then investigate the Drosophila homologue of Ccz1p (which they refer to as Dccz1, encoded by CG14980), which in yeast has been found in a complex with Mon1, but whose functions in endosomal trafficking in metazoans are unknown. When they knock down Dccz1 by using RNA interference, they observe a similar phenotype to loss of Dmon1, suggesting they act in concert. Moreover, depletion of Rab7 also mimics the loss of Dmon1 and Dcc1, further indicating that the loss of Rab7 at late endosomes is responsible for the observed effects. Surprisingly, Dmon1 mutant cells do not have overactive receptor signalling, as would be expected because of the accumulation of receptors, such as Notch, in the maturing endosomes of these cells. This is the case even when receptor uptake into intraluminal vesicles is prevented. This suggests that other mechanisms exist for receptor inactivation.