title: Dmon1 controls recruitment of Rab7 to maturing endosomes in Drosophila.
abstract: The small GTPases Rab5 and Rab7 are important organisers of endosome formation and maturation. In addition, they orchestrate the trafficking of cargo through the endosomal pathway. A crucial event during maturation of endosomes is the replacement of the early organiser Rab5 with the late organiser Rab7 in a process called Rab conversion. Rab conversion is a prerequisite for late events, chief among them the fusion of matured endosomes with the lysosome. Recent work identifies members of the Sand1/Mon1 protein family as crucial factors during this process. Here, we present an analysis of the function of the Drosophila ortholog of mon1/sand1, Dmon1. We found that loss of function of Dmon1 results in an enlargement of maturing endosomes and loss of their association with Rab7. The enlarged endosomes contain Notch and other trans-membrane proteins as cargo. We report the first electron microscopy analysis of Dmon1 cells in a metazoan and extend the analysis of the endosomes in mutant cells. Our results suggest that the phenotype can be explained by the loss of function of Rab7. Moreover, the endosomes of Dmon1 cells mature normally in many aspects, despite the loss of association with Rab7. Surprisingly, we did not observe overactive or ectopic signalling through receptors such as Notch and RTKs in Dmon1 mutant cells, as would have been expected because of the accumulation of receptors in the maturing endosomes of these cells. This was the case even when receptor uptake into intraluminal vesicles was suppressed.
authors: Institut für Genetik, Heinrich-Heine-Universität Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
authors: Jahan
authors: J
authors: Yousefian
authors: Tobias
authors: T
authors: Troost
authors: Ferdi
authors: F
authors: Grawe
authors: Takeshi
authors: T
authors: Sasamura
authors: Mark
authors: M
authors: Fortini
authors: Thomas
authors: T
authors: Klein
mesh_terms: D000818:Animals; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D021381:Protein Transport; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D000090802:rab7 GTP-Binding Proteins
chemical_list: D029721:Drosophila Proteins; D000090802:rab7 GTP-Binding Proteins; D020691:rab GTP-Binding Proteins
keywords: Cell signaling; Mon1; Notch; Rab7; Sand1; endosomal trafficking