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Reconstitution of CUPS in vitro and assessing the mechanism of their cargo packing during unconventional protein secretion

Objective

Most proteins secreted by eukaryotic cells use the endoplasmic reticulum (ER)-to-Golgi pathway of secretion. This is dependent on signal-peptide sequences that ensure protein translocation into the ER and their progress to the cell surface through vesicular flow via the Golgi apparatus. However, a substantial number of proteins that lack a signal-peptide sequence are secreted without entering the classical ER-to-Golgi pathway. Instead they follow the so-called “unconventional pathway of protein secretion”. A well established route within this unconventional pathway refers to cytoplasmic proteins transported to the extracellular environment by autophagosome-like vesicles, such as the Saccharomyces cerevisiae protein Acb1. Secretion of Acb1 in yeast cells is concomitant with the biogenesis of recently characterized membrane structures called CUPS (compartments for unconventional protein secretion) which are thought to function as a sorting platform for Acb1 secretion and possibly for other proteins known to follow similar routes of secretion. The overall aim of this proposal is to further characterize the biogenesis of CUPS in Saccharomyces cerevisiae and to understand their role in the unconventional pathway of secretion, i.e. to address the hypothesis that CUPS are sorting platforms for proteins to be unconventionally secreted. Determining the composition of CUPS, understanding their biogenesis and how their cargo is sorted will surely provide mechanistic insight on how Acb1 and other proteins, which include the inflammatory cytokine IL-1β or Galectin-3 in mammalian cells, are secreted.

Call for proposal

FP7-PEOPLE-2013-IEF
See other projects for this call

Coordinator

FUNDACIO CENTRE DE REGULACIO GENOMICA
EU contribution
€ 166 336,20
Address
CARRER DOCTOR AIGUADER 88
08003 Barcelona
Spain

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Region
Este Cataluña Barcelona
Activity type
Research Organisations
Administrative Contact
Gabriele Picarella (Mr.)
Links
Total cost
No data