A central role for Necl4 (SynCAM4) in Schwann cell-axon interaction and myelination.
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.
Spiegel
Ivo
I
Department of Molecular Cell Biology, The Weizmann Institute of Science, POB 26, Rehovot 76100, Israel.
Adamsky
Konstantin
K
Eshed
Yael
Y
Milo
Ron
R
Sabanay
Helena
H
Sarig-Nadir
Offra
O
Horresh
Ido
I
Scherer
Steven S
SS
Rasband
Matthew N
MN
Peles
Elior
E
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*
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