|Coordinatore||MAX PLANCK GESELLSCHAFT ZUR FOERDERUNG DER WISSENSCHAFTEN E.V.
address: Hofgartenstrasse 8
|Nazionalità Coordinatore||Germany [DE]|
|Totale costo||100˙000 €|
|EC contributo||100˙000 €|
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
|Anno di inizio||2013|
|Periodo (anno-mese-giorno)||2013-04-01 - 2017-03-31|
MAX PLANCK GESELLSCHAFT ZUR FOERDERUNG DER WISSENSCHAFTEN E.V.
address: Hofgartenstrasse 8
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'The Trans Golgi Network (TGN) is the central sorting station for newly synthesised proteins in the cell. Similar to a postal distribution center, incoming cargo is selected, sorted, and packaged to be carried to its final cellular destination by the postman in charge. Due to the involvement of numerous different cargoes and pleiomorhic carriers for the different destinations this process of protein sorting at the TGN is highly sophisticated. While the sorting event of lysosomal hydrolases at the TGN via mannose-6-phosphate receptor and clathrin-coated vesicles to the lysosome is well characterised, the relevant mechanism for other luminal proteins at the TGN remains elusive. We recently discovered a new role for the actin severing protein twinstar in Drosophila and its orthologs in yeast (cof1) and mammalian cells (ADF and cofilin1) in regulation of luminal protein sorting at the TGN. This process is a novel calcium dependent sorting mechanism that directly links the actin cytoskeleton and ADF/cofilin to the TGN localized P-Type calcium ATPase SPCA1. In the project described herein we will characterize the new sorting mechanism in detail. New biochemical tools will identify components of the sorting machinery on both cytosolic and luminal faces of the TGN. Cutting edge Mass Spectrometry will dissect the composition of TGN associated or luminal protein complexes. FLIM experiments will elucidate the temporal and spatial dynamics of the complexes. High throughput screening in yeast will yield new components on a genome wide level. Functional assays utilising siRNA and reconstitution will define their precise role in cargo sorting in vitro and in vivo. The complementary investigation of a Drosophila model will elucidate the physiological relevance of the process in the intact organism and its impact on developmental biology. Altogether, this work represents an essential experimental set up to answer a yet completely unresolved question in cell biology.'
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