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SORTING of ENDOSOMAL AND LYSOSOMAL PROTEINS BY MOLECULAR MACHINERIES

Objective



A major objective of the network is to train young scientists in the most advanced techniques in molecular and cell biology. This will be Cell Biology, the endosomal system and the related biogenesis of accomplished by the creation of post-doctoral fellowships and the rotation lysosomes. Endosomes have occupied a large part of the Cell Biology of the post-doctorals through the different labs of the network. It is scenery since coming into the picture of protein sorting and transport expected that by this rotation the post-doctoral fellows will learn how to twenty years ago (Pesanti and Axline, 1975). Yet, we know very little of design and perform experiments in the fields of molecular and cell the biogenesis, constituents and function of the endosomal system and the biology, biochemistry, protein physicochemistry, and genetics. derived lysosomes.
The project is designed to:
Laboratories with expertise in the manipulation of DNA will teach and help (a) identify the molecular mechanisms involved in the sorting of endosome them in the development of constructs as well as to introduce mutations in and lysosome fated membrane proteins which operate at the plasma proteins to study protein traffic.
membrane, trans-Golgi network, early and late endosomes;
In labs specialised in microscopy they will study the effects of mutations and of exchanging protein domains on the distribution and movement of (b) characterise new compartments that are accessed through vesicles proteins. They will also learn to analyse by NMR and CD the configuration derived from the trans-Golgi network and plasma membrane, and identify the of protein motifs involved in sorting, and to predict and interpret the effect of mutations. Cell biologists will teach them to perform "in vitro" mechanisms that operate in the entrance, retention and exit of proteins from them;
transport assays with which to dissect the machineries involved in (c) establish the extent and links, and characterise the components of vesicle-mediated transport. biochemists and pharmacologists will work with the endocytic and exocytic routes.
them in the identification of the signal transducer mechanisms implicated (d) identify the signal transduction systems involved in the functional in the regulation of protein transport. Finally, together with yeast coupling of the endocytic and exocytic pathways. We expect that these geneticists they will Iearn how to manipulate the yeast genes and will explore in yeast the pathways of protein transport.
studies will help to advance our knowledge on the molecular mechanisms involved in:
(1) the signal mediated endocytosis of proteins and the sorting of proteins at endosomes and the trans-Golgi network, in particular of the signals and mechanisms that operate in their activation, inactivation and decoding;
(3) clathrin-independent endocytosis and in the fusion of the resulting vesicles with early endosomes;
(4) the sorting of proteins in early endosomes and the related biogenesis of carrier vesicles and compartments specialised in the retention and processing of proteins;
(5) the formation of clathrin coated at the trans-Golgi network, the biogenesis of late endosomes;
(6) transfer of materials between early and late endosomes, and the biogenesis of lysosomes;
(7) dynamics of the lysosome;
(8) the direct transport of proteins from the cytosol to lysosomes.

Funding Scheme

NET - Research network contracts

Coordinator

Consejo Superior de Investigaciones Científicas
Address

28049 Madrid - Cantoblanco
Spain

Participants (8)

Consorzio Mario Negri Sud - Centro diRicerche Farmacologiche e Biomediche
Italy
Address
Via Nazionale
66030 Chieti - San Maria Imbaro
Georg-August-Universität Göttingen
Germany
Address
12 D,gosslerstraße
37073 Göttingen
Københavns Universitet
Denmark
Address
3,Blegdamsvej
2200 København
Rijksuniversiteit Utrecht
Netherlands
Address
1,Yalelaan
3508 TD Utrecht
UNIVERSITY COLLEGE LONDON
United Kingdom
Address
Gower Street 5
WC1E 6BT London
Universidad Autónoma de Madrid
Spain
Address

28049 Cantoblanco - Madrid
University of Oslo
Norway
Address

316 Oslo-blindern
Université de Genève
Switzerland
Address
30,Quai E. Ansermet
1211 Genève 4