Nectin-like proteins mediate axon-Schwann cell interactions along the internode and are essential for myelination

• Published in: The Journal of cell biology Vol. 178; no. 5; pp. 861 - 874
• Main Authors: Maurel, Patrice, Einheber, Steven, Galinska, Jolanta, Thaker, Pratik, Lam, Isabel, Rubin, Marina B, Scherer, Steven S, Murakami, Yoshinuri, Gutmann, David H, Salzer, James L
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 27-08-2007; Rockefeller University Press
• Subjects: Animals; Antibodies; Axons; Axons - metabolism; Axons - ultrastructure; Biochemistry; Cell adhesion; Cell Adhesion - physiology; Cell Adhesion Molecules; Cell Adhesion Molecules, Neuronal - genetics; Cell Adhesion Molecules, Neuronal - metabolism; Cells; Cells, Cultured; CHO Cells; Cricetinae; Cricetulus; Ganglia, Spinal - metabolism; Immunoglobulins; Internodes; Mice; Mice, Inbred C57BL; Molecules; Myelin Sheath - metabolism; Myelin Sheath - ultrastructure; Myelination; Nerve Fibers, Myelinated - metabolism; Nerve Fibers, Myelinated - ultrastructure; Neurons; Protein Isoforms - genetics; Protein Isoforms - metabolism; Proteins; Ranvier's Nodes - metabolism; Ranvier's Nodes - ultrastructure; Rats; Ribonucleic acid; RNA; RNA Interference; Schwann cells; Schwann Cells - cytology; Schwann Cells - metabolism; Sciatic Nerve - cytology; Sciatic Nerve - metabolism; Tissues; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.200705132

Axon-glial interactions are critical for the induction of myelination and the domain organization of myelinated fibers. Although molecular complexes that mediate these interactions in the nodal region are known, their counterparts along the internode are poorly defined. We report that neurons and Schwann cells express distinct sets of nectin-like (Necl) proteins: axons highly express Necl-1 and -2, whereas Schwann cells express Necl-4 and lower amounts of Necl-2. These proteins are strikingly localized to the internode, where Necl-1 and -2 on the axon are directly apposed by Necl-4 on the Schwann cell; all three proteins are also enriched at Schmidt-Lanterman incisures. Binding experiments demonstrate that the Necl proteins preferentially mediate heterophilic rather than homophilic interactions. In particular, Necl-1 on axons binds specifically to Necl-4 on Schwann cells. Knockdown of Necl-4 by short hairpin RNA inhibits Schwann cell differentiation and subsequent myelination in cocultures. These results demonstrate a key role for Necl-4 in initiating peripheral nervous system myelination and implicate the Necl proteins as mediators of axo-glial interactions along the internode.