Published online
doi:10.1083/jcb.200705132
The Journal of Cell Biology, Vol. 178, No. 5, 861-874
The Rockefeller University Press, 0021-9525 $30.00
© Maurel et al.
Nectin-like proteins mediate axon–Schwann cell interactions along the internode and are essential for myelination
Patrice Maurel1,
Steven Einheber2,
Jolanta Galinska1,
Pratik Thaker1,
Isabel Lam1,
Marina B. Rubin1,
Steven S. Scherer3,
Yoshinuri Murakami4,
David H. Gutmann5, and
James L. Salzer1
1 Department of Cell Biology and Neurology, Smilow Neuroscience Program, New York University School of Medicine, New York, NY 10016
2 City University of New York, Hunter College, New York, NY 10010
3 Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
4 Department of Cancer Biology, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
5 Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110
Correspondence to Patrice Maurel: maurep01{at}med.nyu.edu; or James L. Salzer: Salzer{at}Saturn.med.nyu.edu
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.
Abbreviations used in this paper: dPBS, Dulbecco's PBS; DRG, dorsal root ganglion; FERM, 4.1, ezrin, radixin, moesin; MAG, myelin-associated glycoprotein; MBP, myelin basic protein; Necl, nectin-like; PDZ, PSD-95, DLG, Z01; PE, phycoerythrin; PNS, peripheral nervous system; shRNA, short hairpin RNA; SynCAM, synaptic cell adhesion molecule; TSLC1, tumor suppressor in lung cancer 1.
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