Thesis – Clémence ROUÉ

Deciphering ADAM10 function in node of Ranvier establishment and in autoimmune nodopathy

Jury

• Laurence GOUTEBROZE, Research Director, Institut de Biologie Paris-Seine, Paris – Reviewer
• Anne-Sophie LIA, Assistant Professor-Hospital Physician, Institut OmegaHealth, Limoges – Reviewer
• Anne DESMAZIERES, Research scientist, Paris Brain Institute – Examiner
• Charbel MASSAAD, Professor, Université Paris Cité – Examiner
• Alexandre JENTZER, Professor-Hospital Physician, IGF, Université de Montpellier – co-supervisor
• Jérôme DEVAUX, Research Director, IGF, University of Montpellier – Thesis supervisor

Summary

Neurofascin-155 (Nfasc155) is a cell adhesion protein that plays an important role in the formation of node of Ranvier and the maintenance of saltatory conduction. Nfasc155 is targeted by autoantibodies in autoimmune nodopathy, leading to motor and sensory deficits. We recently discovered that ADAM10, a metalloprotease, is expressed at the node of Ranvier. We sought to determine whether ADAM10 contributes to the formation of the node of Ranvier by cleaving nodal and paranodal proteins. We demonstrated that Nfasc155 is cleaved by ADAM10 in myelinating glial cells ex vivo. Since the degradation of Nfasc155 appears to be responsible for the paranodal alterations observed in autoimmune nodopathy, we demonstrated the involvement of ADAM10 in the pathophysiology of autoimmune nodopathy in vivo.