title: Schwannomin-interacting Protein 1 Isoform IQCJ-SCHIP1 Is a Multipartner Ankyrin- and Spectrin-binding Protein Involved in the Organization of Nodes of Ranvier.
abstract: The nodes of Ranvier are essential regions for action potential conduction in myelinated fibers. They are enriched in multimolecular complexes composed of voltage-gated Nav and Kv7 channels associated with cell adhesion molecules. Cytoskeletal proteins ankyrin-G (AnkG) and βIV-spectrin control the organization of these complexes and provide mechanical support to the plasma membrane. IQCJ-SCHIP1 is a cytoplasmic protein present in axon initial segments and nodes of Ranvier. It interacts with AnkG and is absent from nodes and axon initial segments of βIV-spectrin and AnkG mutant mice. Here, we show that IQCJ-SCHIP1 also interacts with βIV-spectrin and Kv7.2/3 channels and self-associates, suggesting a scaffolding role in organizing nodal proteins. IQCJ-SCHIP1 binding requires a βIV-spectrin-specific domain and Kv7 channel 1-5-10 calmodulin-binding motifs. We then investigate the role of IQCJ-SCHIP1in vivoby studying peripheral myelinated fibers inSchip1knock-out mutant mice. The major nodal proteins are normally enriched at nodes in these mice, indicating that IQCJ-SCHIP1 is not required for their nodal accumulation. However, morphometric and ultrastructural analyses show an altered shape of nodes similar to that observed in βIV-spectrin mutant mice, revealing that IQCJ-SCHIP1 contributes to nodal membrane-associated cytoskeleton organization, likely through its interactions with the AnkG/βIV-spectrin network. Our work reveals that IQCJ-SCHIP1 interacts with several major nodal proteins, and we suggest that it contributes to a higher organizational level of the AnkG/βIV-spectrin network critical for node integrity.
authors.affiliation: From INSERM, UMR-S 839, F-75005 Paris.|the Université Pierre et Marie Curie (UPMC)-Sorbonne Universités, UMR-S 839, 75005 Paris.|the Institut du Fer à Moulin, 75005 Paris, and.
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Martin
authors.affiliation: From INSERM, UMR-S 839, F-75005 Paris.|the Université Pierre et Marie Curie (UPMC)-Sorbonne Universités, UMR-S 839, 75005 Paris.|the Institut du Fer à Moulin, 75005 Paris, and.
authors.forename: Carmen
authors.initials: C
authors.lastname: Cifuentes-Diaz
authors.affiliation: the Aix Marseille University, CNRS, CRN2M, 13344 Marseille, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Devaux
authors.affiliation: From INSERM, UMR-S 839, F-75005 Paris.|the Université Pierre et Marie Curie (UPMC)-Sorbonne Universités, UMR-S 839, 75005 Paris.|the Institut du Fer à Moulin, 75005 Paris, and.
authors.forename: Marta
authors.initials: M
authors.lastname: Garcia
authors.affiliation: From INSERM, UMR-S 839, F-75005 Paris.|the Université Pierre et Marie Curie (UPMC)-Sorbonne Universités, UMR-S 839, 75005 Paris.|the Institut du Fer à Moulin, 75005 Paris, and.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Bureau
authors.affiliation: From INSERM, UMR-S 839, F-75005 Paris.|the Université Pierre et Marie Curie (UPMC)-Sorbonne Universités, UMR-S 839, 75005 Paris.|the Institut du Fer à Moulin, 75005 Paris, and.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Thomasseau
authors.affiliation: From INSERM, UMR-S 839, F-75005 Paris.|the Université Pierre et Marie Curie (UPMC)-Sorbonne Universités, UMR-S 839, 75005 Paris.|the Institut du Fer à Moulin, 75005 Paris, and.
authors.forename: Esther
authors.initials: E
authors.lastname: Klingler
authors.affiliation: From INSERM, UMR-S 839, F-75005 Paris.|the Université Pierre et Marie Curie (UPMC)-Sorbonne Universités, UMR-S 839, 75005 Paris.|the Institut du Fer à Moulin, 75005 Paris, and.
authors.forename: Jean-Antoine
authors.initials: JA
authors.lastname: Girault
authors.affiliation: the Université Pierre et Marie Curie (UPMC)-Sorbonne Universités, UMR-S 839, 75005 Paris, laurence.goutebroze@inserm.fr.|the Institut du Fer à Moulin, 75005 Paris, and.
authors.forename: Laurence
authors.initials: L
authors.lastname: Goutebroze
mesh_terms: D000818:Animals; D017487:Ankyrins / Q000378:metabolism*; D001704:Biopolymers / Q000378:metabolism; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002522:Chlorocebus aethiops; D051379:Mice; D008817:Mice, Mutant Strains; D009043:Motor Activity; D017933:Peripheral Nervous System / Q000502:physiology / Q000648:ultrastructure; D011901:Ranvier's Nodes / Q000378:metabolism*
chemical_list: D017487:Ankyrins; D001704:Biopolymers; D002352:Carrier Proteins; C000600131:SCHIP1 protein, mouse; C025957:spectrin-binding proteins
keywords: SCHIP1; animal model; axon; electron microscopy (EM); immunohistochemistry; nodal shape architecture; peripheral myelinated fibers; potassium channel; protein-protein interaction; spectrin