PuSH - Publikationsserver des Helmholtz Zentrums München

Rowshanravan, B.* ; Woodcock, S.A.* ; Botella, J.A.* ; Kiermayer, C. ; Schneuwly, S.* ; Hughes, D.A.*

RasGAP mediates neuronal survival in Drosophila through direct regulation of Rab5-dependent endocytosis.

J. Cell Sci. 127, 2849-2861 (2014)
Verlagsversion DOI
Free by publisher
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
The GTPase Ras can either promote or inhibit cell survival. Inactivating mutations in RasGAP (vap), a Ras GTPase-activating protein, lead to age-related brain degeneration in Drosophila. Genetic interactions implicate the epidermal growth factor receptor (EGFR)-Ras pathway in promoting neurodegeneration but the mechanism is not known. Here we show that the Src homology 2 (SH2) domains of RasGAP are essential for its neuroprotective function. By using affinity purification and mass spectrometry, we identify a complex containing RasGAP together with Sprint, a Ras effector and putative activator of the endocytic GTPase Rab5. Formation of the RasGAP-Sprint complex requires the SH2 domains of RasGAP and tyrosine phosphorylation of Sprint. RasGAP and Sprint co-localize with Rab5-positive early endosomes but not with Rab7-positive late endosomes. We demonstrate a key role for this interaction in neurodegeneration: mutation of Sprint (or Rab5) suppresses neuronal cell death caused by the loss of RasGAP. These results indicate that the long-term survival of adult neurons in Drosophila is critically dependent on the activities of two GTPases, Ras and Rab5, regulated by the interplay of RasGAP and Sprint.
Weitere Metriken?
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Tyrosine Phosphorylation ; Sprint ; Guanine-nucleotide-exchange Factor ; Rab5 ; Drosophila ; Rasgap ; Vap; Nucleotide Exchange Factor; Gtpase-activating Protein; Programmed Cell-death; Growth-factor; Gene-expression; Nervous-system; Rab5 Effector; Migration; Pathway; Melanogaster
ISSN (print) / ISBN 0021-9533
e-ISSN 1477-9137
Quellenangaben Band: 127, Heft: 13, Seiten: 2849-2861 Artikelnummer: , Supplement: ,
Verlag Company of Biologists
Verlagsort Cambridge
Begutachtungsstatus Peer reviewed