Anti‐β1 integrin antibody inhibits schwann cell meylination

Cristina Fernandez‐Valle, Lisa Gwynn, Patrick M. Wood, Salvatore Carbonetto, Mary Bartlett Bunge

Research output: Contribution to journalArticle

102 Scopus citations

Abstract

Schwann cells (SCs) co-cultured with sensory neurons require ascorbate supplementation for basal lamina assembly and differentiation into myelinating cells. The ascorbate requirement can be bypassed by adding a purified basal lamina component, laminin, to SC/neuron co-cultures. We have examined the role of laminin receptors, namely, the β1 subfamily of integrins, in the process of myelination. We demonstrate by immunostaining or immunoprecipitation that undifferentiated SCs in contact with axons express large amounts of the β1 subunit in association with the α1 or α6 subunit. In co-cultures of myelinating SCs, α1β1 is no longer present, α6β1 is still present but at reduced levels, and α6β4 is expressed at much higher levels than in co-cultures of undifferentiated SCs. Immunogold labelling at the electron microscope level suggested that β1 integrins are randomly distributed on undifferentiated SCs, become localized to the SC surface contacting basal lamina in differentiating SCs before the onset of myelination, and are not detected on myelinating SCs. Fab fragments of β1 function-blocking antibody block both attachment of isolated SCs to laminin and formation of myelin sheaths by SCs co-cultured with neurons in ascorbate- supplemented medium. SCs unable to myelinate in the presence of the anti-β1 antibody assemble patchy basal lamina that is only loosely attached to the cell surface and in some cases appears to be detaching from the membrane. In contrast, an α1β1 function-blocking antibody only partially blocks attachment of isolated SCs to laminin but has no inhibitory effect on SC myelination. These results are consistent with the hypothesis that a member of the β1 subfamily of integrins other than α1β1 binds laminin present in basal lamina to the SC surface and transduces signals that are critical for initiation of SC differentiation into a myelinating cell.

Original languageEnglish (US)
Pages (from-to)1207-1226
Number of pages20
JournalJournal of Neurobiology
Volume25
Issue number10
DOIs
StatePublished - Oct 1994

Keywords

  • β1 integrins
  • basal lamina
  • differentiation
  • myelin
  • Schwann cells

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Fernandez‐Valle, C., Gwynn, L., Wood, P. M., Carbonetto, S., & Bunge, M. B. (1994). Anti‐β1 integrin antibody inhibits schwann cell meylination. Journal of Neurobiology, 25(10), 1207-1226. https://doi.org/10.1002/neu.480251004