Fiche publication
Date publication
novembre 2013
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DE ARCANGELIS Adèle
Tous les auteurs :
Pellegatta M, De Arcangelis A, D'Urso A, Nodari A, Zambroni D, Ghidinelli M, Matafora V, Williamson C, Georges-Labouesse E, Kreidberg J, Mayer U, McKee KK, Yurchenco PD, Quattrini A, Wrabetz L, Feltri ML
Lien Pubmed
Résumé
During development, Schwann cells extend lamellipodia-like processes to segregate large- and small-caliber axons during the process of radial sorting. Radial sorting is a prerequisite for myelination and is arrested in human neuropathies because of laminin deficiency. Experiments in mice using targeted mutagenesis have confirmed that laminins 211, 411, and receptors containing the beta1 integrin subunit are required for radial sorting; however, which of the 11 alpha integrins that can pair with beta1 forms the functional receptor is unknown. Here we conditionally deleted all the alpha subunits that form predominant laminin-binding beta1 integrins in Schwann cells and show that only alpha6beta1 and alpha7beta1 integrins are required and that alpha7beta1 compensates for the absence of alpha6beta1 during development. The absence of either alpha7beta1 or alpha6beta1 integrin impairs the ability of Schwann cells to spread and to bind laminin 211 or 411, potentially explaining the failure to extend cytoplasmic processes around axons to sort them. However, double alpha6/alpha7 integrin mutants show only a subset of the abnormalities found in mutants lacking all beta1 integrins, and a milder phenotype. Double-mutant Schwann cells can properly activate all the major signaling pathways associated with radial sorting and show normal Schwann cell proliferation and survival. Thus, alpha6beta1 and alpha7beta1 are the laminin-binding integrins required for axonal sorting, but other Schwann cell beta1 integrins, possibly those that do not bind laminins, may also contribute to radial sorting during peripheral nerve development.
Référence
J Neurosci. 2013 Nov 13;33(46):17995-8007
