ELANSCI

Role of Lgi and Adam proteins in nerve development and function

Coordinatore	ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM    more  Organization address address: 's Gravendijkwal 230 city: ROTTERDAM postcode: 3015CE contact info Titolo: Ms. Nome: Nuran Cognome: Tuzen Email: send email Telefono: -7043190 Fax: -7044722
Nazionalità Coordinatore	Netherlands [NL]
Totale costo	161˙162 €
EC contributo	161˙162 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-IEF-2008
Funding Scheme	MC-IEF
Anno di inizio	2009
Periodo (anno-mese-giorno)	2009-07-01   -   2011-10-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM  Organization address address: 's Gravendijkwal 230 city: ROTTERDAM postcode: 3015CE contact info Titolo: Ms. Nome: Nuran Cognome: Tuzen Email: send email Telefono: -7043190 Fax: -7044722	NL (ROTTERDAM)	coordinator	161˙162.47

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 Obiettivo del progetto (Objective)

'Schwann cells (SC) are the most important accessory cells to neurons in the peripheral nervous system (PNS) and are involved in every aspect of nerve structure, function and regeneration. Dr Meijer’s group has identified a novel SC expressed factor, Lgi4, involved in nerve development and function. The Lgi4 gene is mutated in a natural mouse mutant called Claw Paw, which exhibits delayed axonal sorting and hypomyelination in the PNS. Lgi4 is a member of a small family of secreted proteins mainly expressed in the nervous system. While mutations in Lgi1 have been implicated in epilepsy in humans, virtually nothing is known about the other two members of the family; Lgi2 and Lgi3. These genes are expressed during development in primary sensory neurons, suggesting that they, together with Lgi4, are involved in diverse aspects of development and function of the PNS. Some or all of these functions could be mediated through interaction with members of the Adam (A Disintergin And Metalloprotease) family of transmembrane proteins. It has been demonstrated that Lgi1 binds to the metalloprotease inactive member Adam22. Recent results from the host laboratory have demonstrated that Lgi4, 2 and 3 also bind Adam22. Adam22 mutant mice have a phenotype that resembles that of Lgi4 mutant mice, suggesting a possible interaction during nerve development. The cellular processes and molecular mechanisms that are influenced by this interaction are at present unclear. Therefore, the major aim of this research proposal is to unravel the cellular and molecular mechanisms through which Lgi4-Adam22 interaction contributes to proper axonal sorting and myelin formation. Insight into the role of Lgi proteins in peripheral nerve development will be instrumental in developing novel therapeutic strategies to aid nerve repair and function and, in addition, will inform us about the role these proteins play in eleptogenesis.'