Cargando…

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

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 Sc...

Descripción completa

Detalles Bibliográficos
Autores principales: Maurel, Patrice, Einheber, Steven, Galinska, Jolanta, Thaker, Pratik, Lam, Isabel, Rubin, Marina B., Scherer, Steven S., Murakami, Yoshinuri, Gutmann, David H., Salzer, James L.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064549/
https://www.ncbi.nlm.nih.gov/pubmed/17724124
http://dx.doi.org/10.1083/jcb.200705132
_version_ 1782137563675361280
author Maurel, Patrice
Einheber, Steven
Galinska, Jolanta
Thaker, Pratik
Lam, Isabel
Rubin, Marina B.
Scherer, Steven S.
Murakami, Yoshinuri
Gutmann, David H.
Salzer, James L.
author_facet Maurel, Patrice
Einheber, Steven
Galinska, Jolanta
Thaker, Pratik
Lam, Isabel
Rubin, Marina B.
Scherer, Steven S.
Murakami, Yoshinuri
Gutmann, David H.
Salzer, James L.
author_sort Maurel, Patrice
collection PubMed
description 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.
format Text
id pubmed-2064549
institution National Center for Biotechnology Information
language English
publishDate 2007
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-20645492008-02-27 Nectin-like proteins mediate axon–Schwann cell interactions along the internode and are essential for myelination Maurel, Patrice Einheber, Steven Galinska, Jolanta Thaker, Pratik Lam, Isabel Rubin, Marina B. Scherer, Steven S. Murakami, Yoshinuri Gutmann, David H. Salzer, James L. J Cell Biol Research Articles 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. The Rockefeller University Press 2007-08-27 /pmc/articles/PMC2064549/ /pubmed/17724124 http://dx.doi.org/10.1083/jcb.200705132 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Maurel, Patrice
Einheber, Steven
Galinska, Jolanta
Thaker, Pratik
Lam, Isabel
Rubin, Marina B.
Scherer, Steven S.
Murakami, Yoshinuri
Gutmann, David H.
Salzer, James L.
Nectin-like proteins mediate axon–Schwann cell interactions along the internode and are essential for myelination
title Nectin-like proteins mediate axon–Schwann cell interactions along the internode and are essential for myelination
title_full Nectin-like proteins mediate axon–Schwann cell interactions along the internode and are essential for myelination
title_fullStr Nectin-like proteins mediate axon–Schwann cell interactions along the internode and are essential for myelination
title_full_unstemmed Nectin-like proteins mediate axon–Schwann cell interactions along the internode and are essential for myelination
title_short Nectin-like proteins mediate axon–Schwann cell interactions along the internode and are essential for myelination
title_sort nectin-like proteins mediate axon–schwann cell interactions along the internode and are essential for myelination
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064549/
https://www.ncbi.nlm.nih.gov/pubmed/17724124
http://dx.doi.org/10.1083/jcb.200705132
work_keys_str_mv AT maurelpatrice nectinlikeproteinsmediateaxonschwanncellinteractionsalongtheinternodeandareessentialformyelination
AT einhebersteven nectinlikeproteinsmediateaxonschwanncellinteractionsalongtheinternodeandareessentialformyelination
AT galinskajolanta nectinlikeproteinsmediateaxonschwanncellinteractionsalongtheinternodeandareessentialformyelination
AT thakerpratik nectinlikeproteinsmediateaxonschwanncellinteractionsalongtheinternodeandareessentialformyelination
AT lamisabel nectinlikeproteinsmediateaxonschwanncellinteractionsalongtheinternodeandareessentialformyelination
AT rubinmarinab nectinlikeproteinsmediateaxonschwanncellinteractionsalongtheinternodeandareessentialformyelination
AT schererstevens nectinlikeproteinsmediateaxonschwanncellinteractionsalongtheinternodeandareessentialformyelination
AT murakamiyoshinuri nectinlikeproteinsmediateaxonschwanncellinteractionsalongtheinternodeandareessentialformyelination
AT gutmanndavidh nectinlikeproteinsmediateaxonschwanncellinteractionsalongtheinternodeandareessentialformyelination
AT salzerjamesl nectinlikeproteinsmediateaxonschwanncellinteractionsalongtheinternodeandareessentialformyelination