A trimeric metazoan Rab7 GEF complex is crucial for endocytosis and scavenger function
Autor(en): | Dehnen, Lena Janz, Maren Verma, Jitender Kumar Psathaki, Olympia Ekaterini Langemeyer, Lars Frohlich, Florian Heinisch, Jurgen J. Meyer, Heiko Ungermann, Christian Paululat, Achim |
Stichwörter: | Cell Biology; Drosophila; DROSOPHILA-MELANOGASTER; ENDOSOME; GARLAND CELL; GEF; GTPASE YPT7; IDENTIFICATION; LYSOSOME; Mon1-Ccz1 complex; MON1-CCZ1 GEF; NEPHROCYTES; PERICARDIAL CELLS; ULTRASTRUCTURE | Erscheinungsdatum: | 2020 | Herausgeber: | COMPANY BIOLOGISTS LTD | Journal: | JOURNAL OF CELL SCIENCE | Volumen: | 133 | Ausgabe: | 13 | Zusammenfassung: | 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 guanine-nucleotide-exchange factor (GEF). Here, we show that full function of the Drosophila Mon1-Ccz1 complex requires a third stoichiometric subunit, termed Bulli (encoded by CG8270). 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, (iii) defective Rab7 localisation and (iv) impaired endosomal maturation. Moreover, longevity of animals lacking bulli is affected. Both the Mon1-Ccz1 dimer and a Bullicontaining trimer display Rab7 GEF activity. In summary, this suggests a key role for Bulli in the Rab5 to Rab7 transition during endosomal maturation rather than a direct influence on the GEF activity of Mon1-Ccz1. |
ISSN: | 00219533 | DOI: | 10.1242/jcs.247080 |
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geprüft am 29.04.2024