MUPS

Mechanism of Unconventional Protein Secretion

Coordinatore	FUNDACIO CENTRE DE REGULACIO GENOMICA    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Spain [ES]
Totale costo	2˙206˙963 €
EC contributo	2˙206˙963 €
Programma	FP7-IDEAS-ERC Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	ERC-2010-AdG_20100317
Funding Scheme	ERC-AG
Anno di inizio	2011
Periodo (anno-mese-giorno)	2011-08-01   -   2016-07-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	FUNDACIO CENTRE DE REGULACIO GENOMICA  Organization address address: CARRER DOCTOR AIGUADER 88 city: BARCELONA postcode: 8003 contact info Titolo: Dr. Nome: Vivek Cognome: Malhotra Email: send email Telefono: +34 93 3160235 Fax: +34 93 3160099	ES (BARCELONA)	hostInstitution	2˙206˙963.00
2	FUNDACIO CENTRE DE REGULACIO GENOMICA  Organization address address: CARRER DOCTOR AIGUADER 88 city: BARCELONA postcode: 8003 contact info Titolo: Mr. Nome: Gabriele Cognome: Picarella Email: send email Telefono: +34 93 3160234 Fax: +34 93 3969983	ES (BARCELONA)	hostInstitution	2˙206˙963.00

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 Obiettivo del progetto (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.'