Open AccessA trimeric metazoan Rab7 GEF complex is crucial for endocytosis and scavenger function
Author(s) -
Lena Dehnen,
Maren Janz,
Jaya Verma,
Olympia E. Psathaki,
Lars Langemeyer,
Florian Fröhlich,
Jürgen J. Heinisch,
Heiko Meyer,
Christian Ungermann,
Achim Paululat
Publication year - 2020
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.247080
Subject(s) - endosome , biology , microbiology and biotechnology , guanine nucleotide exchange factor , biogenesis , endocytosis , function (biology) , biochemistry , intracellular , gtpase , cell , gene
Endosome biogenesis in eukaryotic cells is critical for nutrient uptake and plasma membrane integrity. Early endosomes initially contain Rab5, which is replaced by Rab7 on late endosomes prior to their fusion with lysosomes. Recruitment of Rab7 to endosomes requires the Mon1-Ccz1 guanosine exchange factor (GEF). Here, we show that full function of the Drosophila Mon1-Ccz1 complex requires a third stoichiometric subunit, termed Bulli. Bulli localises to Rab7 positive endosomes, in agreement with its function in the GEF complex. Using Drosophila nephrocytes as a model system, we observe that absence of Bulli results in (i) reduced endocytosis, (ii) Rab5 accumulation within non-acidified enlarged endosomes, and (iii) defective Rab7 localisation and (iv) impaired endosomal maturation. Moreover, longevity of animals lacking bulli is affected. Both Mon1-Ccz1 dimer and a Bulli-containing trimer display Rab7 GEF activity. In summary, this suggests a key role of Bulli in Rab5 to Rab7 transition during endosomal maturation rather than a direct influence on the GEF activity of Mon1-Ccz1.