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Content archived on 2024-05-29

Role of microtubule plus-end tracking proteins in synaptogenesis

Objective

Plus-end tracking proteins, or +TIPs, are microtubule (MT) binding proteins that specifically associate with the distal ends of MTs. +TIPs are both involved in the regulation of MT dynamics and intracellular membrane transport over MTs. Since +TIPs are import ant mediators of MT dynamics during axonal growth, we speculate that they might also have a role in the establishment of synaptic contacts. This will be addressed by using +TIP knockout mice as model systems for abnormal synaptic formation and/or stabilization. Our studies will be performed in primary hippocampal neuronal cultures from these mice and will be supported by siRNA experiments.

The finding of abnormal synaptic contacts in +TIP deficient cells might be due to a deregulation of MT dynamics and/or to altered transport of synaptic proteins. Both questions will be addressed by using immuno-fluorescence time-lapse microscopy and by the use of a new microscope that allows the analysis of vesicle movement in living cells. Finally, we will study how distinct signal ling pathways involving the kinases GSK-3 and Abl lead to +TIP-mediated local rearrangements of MTs.

Biochemical studies will be performed in neuroblastoma and non-neuronal cell lines. The role of these signalling pathways during synaptogenesis will be evaluated in cultures of mossy fibres stimulated with Wnt7a. We expect that the results obtained from this project will help to improve our understanding of +TIP function during the highly complex process of synapse formation.

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Topic(s)

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Call for proposal

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FP6-2002-MOBILITY-11
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Funding Scheme

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ERG - Marie Curie actions-European Re-integration Grants

Coordinator

ERASMUS MC
EU contribution
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Total cost

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