MOLECULAR DISSECTION of THE REGULATED SECRETORY PATHWAY IN NEUROEND OCRINE CELLS : PROTEIN SORTING and SECRETORY GRANULE FORMATION

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Project objective

European post-doctoral fellows will be appointed for three years and dependent on neuropeptides and peptide hormones that are generated through trained in biochemical, molecular biological and cell biological proteolytic cleavage of larger precursor proteins (prohormones) in the techniques. To acquire expertise with specialised techniques in this field, secretory pathway of neuroendocrine cells. These cells are equipped with the post-docs will visit or interact with the other participating laboratories. Each participating group has the facilities and personnel two pathways of secretion; in the regulated pathway the prohormone-derived compatible with the aim of providing a proper training environment for the peptides are produced and stored in secretory granules until an appropriate extracellular stimulus reaches the cell, while in the constitutive pathway postdocs. material is rapidly transported in vesicles from the Golgi to the surface of the cell. Prohormones and other proteins destined for regulated secretion are selectively sorted away from the bulk of constitutively secreted proteins in the trans-Golgi network (TGN), the site where the granules are also formed. A gap in our knowledge about secretory pathways concerns the molecular events occurring during protein sorting in the TGN and formation of the secretory granules. To deal with this complex research topic, eight groups from seven different European countries will intensively collaborate in the proposed Network and will combine their highly qualified research experiences and facilities in a multidisciplinary approach. Our main research goals will be to obtain a better understanding of: (i) the role of specific sequences within regulated secretory proteins, and the contribution of members of the granin family of neuroendocrine proteins, in facilitating sorting within the TGN; and (ii) the role of protein aggregation, and the involvement of cytosolic and membrane proteins, in protein sorting and secretory granule formation. Furthermore, these processes in neuroendocrine cells will be compared with similar mechanisms operating in the regulated secretory pathway of exocrine cells. The proposed studies will enhance our knowledge of neuroendocrine cell biology and contribute to a better understanding of a wide variety of neurological and endocrine disorders which have been linked to a malfunctioning of the secretory pathway.

Original text from CORDIS.

Participants

• Katholieke Universiteit Nijmegen · NijmegenCoordinatorNetherlands
• Consorzio Milano Ricerche · MilanoItaly
• INSTITUT NATIONAL DE LA RECHERCHE AGRONOMIQUE (INRA) · PARISFrance
• Imperial Cancer Research Fund · LondonUnited Kingdom
• KATHOLIEKE UNIVERSITEIT LEUVEN · LEUVENBelgium
• RUPRECHT-KARLS-UNIVERSITÄT HEIDELBERG · HEIDELBERGGermany
• UNIVERSITE DE GENEVE · GENEVE 4Switzerland
• UNIVERSITY OF ABERDEEN · ABERDEENUnited Kingdom

Links

• View on CORDIS