Characterisation of arrestin-like proteins in ESCRT mediated processes

• Antragstellerin: Dr. Susanne Rauch
• Fachliche Zuordnung: Zellbiologie
• Förderung: Förderung von 2010 bis 2013
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 167759311

The ESCRT machinery consists of a highly conserved set of protein complexes, ESCRT 0, I, II and III that functions in endosomal cargo sorting, midbody abscission during cytokinesis and viral budding. Enveloped viruses hijack the ESCRT pathway via short peptide motifs (L- (late) domains) to promote viral budding by engaging the ESCRTIII membrane scission activity. The PPXY L-domain present in viruses like MLV (murine leukemia virus) interacts with HECT ubiquitin ligases. However, it remains unclear how recruitment of ESCRTIII takes place. Several lines of evidence point to the existence of an unidentified cellular adaptor between HECT ubiquitin ligases and the ESCRT machinery. In this project, I will test the arrestin-like family of proteins, regulators of receptor endocytosis in yeast, for their ability to provide this missing link. Preliminary results show that arrestin-like proteins are able to interact with ubiquitin ligases and ESCRT components. On this basis, I will analyse the role of arrestin-like proteins in PPXY motif dependent budding as well as endosomal sorting. Furthermore, preliminary results argue for the existence of an unknown binding partner of arrestin-like proteins involved in interactions with the ESCRT pathway. Further studies will thus be aimed at the identification of this factor and its role in ESCRT mediated processes. In summary, this project has the potential to identify proteins involved in PPXY L-domain mediated budding and will allow further insights the composition of the ESCRT machinery and the cell biology of MVB biogenesis.

• DFG-Verfahren: Forschungsstipendien
• Internationaler Bezug: Großbritannien
• Gastgeber: Dr. Juan Martin-Serrano