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Content archived on 2024-06-18

Characterization of a novel sorting pathway at the Trans Golgi Network (TGN)

Objective

"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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Topic(s)

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Call for proposal

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FP7-PEOPLE-2012-CIG
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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.

MC-CIG - Support for training and career development of researcher (CIG)

Coordinator

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
EU contribution
€ 100 000,00
Address
HOFGARTENSTRASSE 8
80539 Munchen
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Research Organisations
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Total cost

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.

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