PSA-NCAM-AX · Interactions between soluble factors and NCAM isoforms and role of the carbohydrate PolySialicAcid (PSA) in the control of axonal growth and guidance.
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2005-06-01 → 2006-08-31
- EU contribution
- €80,000
- Participants
- 1
- Scheme
- IRG
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Project objective
The immunoglobulin super family adhesion molecule NCAM is implicated in cell migration, axonal outgrowth, and synaptic plasticity under normal or pathological situations. Recently, NCAM was demonstrated to physically interact with the growth factor GDNF a soluble factor also active in modulating axonal migration. In my research project, I will examine: the mechanisms by which GDNF interacts with NCAM and how PSA, the polysialic posttranslational modification of NCAM, is able to regulate NCAM activity. For this purpose, I will develop two approaches: 1. I will observe the localization, trafficking and recycling of NCAM isoforms, NCAM140 and NCAM180, during neuronal development and cell migration and I will investigate the effect of GDNF on NCAM movements and relocalization. I will observe the two NCAM isoforms, NCAM140 and NCAM180 simultaneously and test whether their dynamic is specific, and if they respond differently to GDNF. 2. I will also observe whether PSA is capable of regulating the NCAM dynamics, and I will study the effects of this posttranslational modification on the binding of NCAM to several known interacting proteins. I will also focused on the lipid raft and determine whereas these microdomains enriched in potent effectors of signal transduction are essential for the physical interaction of NCAM to GFR and GDNF and therefore for the signalling initiated by this interaction. For this work, I will use culture of dissociated neurons, from NCAM- or PSA-deficient or GFP-NCAM mice. Cell imaging technologies such as time-lapse and FRET system will be used to monitor the proteins in living neurons. In addition biochemical approaches will help to identify the PSA-dependent NCAM-interacting proteins. A long-term interest will be to understand how these molecules act in neurodegenerative diseases as well as in the regeneration of injured neuronal tissues and whether they may constitute therapeutic targets.
Original text from CORDIS.
Participants
- CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE · PARISCoordinatorFrance
Links
Data: CORDIS, © European Union