title: A central role for Necl4 (SynCAM4) in Schwann cell-axon interaction and myelination.
abstract: Myelination in the peripheral nervous system requires close contact between Schwann cells and the axon, but the underlying molecular basis remains largely unknown. Here we show that cell adhesion molecules (CAMs) of the nectin-like (Necl, also known as SynCAM or Cadm) family mediate Schwann cell-axon interaction during myelination. Necl4 is the main Necl expressed by myelinating Schwann cells and is located along the internodes in direct apposition to Necl1, which is localized on axons. Necl4 serves as the glial binding partner for axonal Necl1, and the interaction between these two CAMs mediates Schwann cell adhesion. The disruption of the interaction between Necl1 and Necl4 by their soluble extracellular domains, or the expression of a dominant-negative Necl4 in Schwann cells, inhibits myelination. These results suggest that Necl proteins are important for mediating axon-glia contact during myelination in peripheral nerves.
authors.affiliation: Department of Molecular Cell Biology, The Weizmann Institute of Science, POB 26, Rehovot 76100, Israel.
authors.forename: Ivo
authors.initials: I
authors.lastname: Spiegel
authors.forename: Konstantin
authors.initials: K
authors.lastname: Adamsky
authors.forename: Yael
authors.initials: Y
authors.lastname: Eshed
authors.forename: Ron
authors.initials: R
authors.lastname: Milo
authors.forename: Helena
authors.initials: H
authors.lastname: Sabanay
authors.forename: Offra
authors.initials: O
authors.lastname: Sarig-Nadir
authors.forename: Ido
authors.initials: I
authors.lastname: Horresh
authors.forename: Steven S
authors.initials: SS
authors.lastname: Scherer
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Rasband
authors.forename: Elior
authors.initials: E
authors.lastname: Peles
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D019556:COS Cells; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal / Q000502:physiology*; D002522:Chlorocebus aethiops; D005455:Fluorescent Antibody Technique; D007136:Immunoglobulins; D008297:Male; D008854:Microscopy, Electron; D009186:Myelin Sheath / Q000502:physiology*; D017933:Peripheral Nervous System / Q000502:physiology; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics / Q000502:physiology; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012583:Schwann Cells / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000502:physiology*
chemical_list: C465040:Cadm1 protein, rat; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D007136:Immunoglobulins; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D012313:RNA