Objective
Approximately 30% of the human genes encode proteins that enter the Endoplasmic Reticulum (ER) by a hydrophobic sequence called the signal sequence. Most of these proteins are transported to the Golgi apparatus for sorting and subsequent delivery to the endosomes, cell surface, and the extracellular space. There is good understanding of this process of ¿conventional¿ protein secretion. Surprisingly, there is another class of cytoplasmic proteins that are secreted even though they a lack signal sequence to enter the ER. How are such proteins secreted? The yeast protein a-factor achieves this goal by direct transport across the plasma membrane via an ABC transporter encoded by the STE6 gene. Little else of significance is known about this ¿unconventional¿ secretory pathway.
Our new findings reveal that secretion of signal sequence lacking acyl-coA binding protein or Acb1 in Saccharomyces cerevisae and Pichia pastoris requires autophagy related genes, fusion of membranes with early endosomes, formation of multivesicular body and the plasma membrane fusion protein (t-SNARE) called Sso1p. Our results indicate that secretion of Acb1 is mediated by a secretory autophagosomes. The secretion of Acb1 therefore does not follow the same pathway as the a-factor. But how is Acb1 packed into an autophagosome and why doesn¿t the secretory autophagosome fuse with the vacuole? In other words what is the difference between a secretory and a degradative autophagosome? Does an autophagosome-like vesicle also secrete cytokines, which lack a signal sequence to enter the ER? Our aim is to address these key questions. Many unconventionally secreted proteins regulate tissue organization, behavior (anxiety and addiction), angiogenesis, immune surveillance and diabetes. Understanding the mechanism of this poorly understood process is therefore of fundamental importance.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine endocrinology diabetes
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
ERC-2010-AdG_20100317
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Host institution
08003 Barcelona
Spain
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.