Editors' ChoiceEphrins

From Axon Guidance to Neurite Inhibitor to Viral Receptor

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Science's STKE  02 Aug 2005:
Vol. 2005, Issue 295, pp. tw281
DOI: 10.1126/stke.2952005tw281

Two groups report activities for ephrins beyond axon guidance and cell migration. Bonaparte et al. performed a microarray screen comparing cells that were permissive and nonpermissive for Nipah virus (NiV)- or Hendra virus (HeV)-mediated cell fusion (a surrogate measure of infection) and identified ephrin B2 (EFNB2), whose mRNA was abundant in fusogenic cells. When expressed in nonfusogenic cells, EFNB2 rendered those cells competent for HeV-mediated fusion. A soluble Fc fusion protein (EFNB2/Fc) blocked HeV- and NiV-stimulated cell fusion of EFNB2-transfected cells, and this fusion protein coimmunoprecipitated and interacted with soluble forms of the attachment glycoprotein (sG) from the two viruses in surface plasmon resonance assays. Viral infection was also assayed; EFNB2/Fc prevented HeV and NiV infection in permissive cells, and EFNB2 was sufficient to allow infection by HeV and NiV when transfected into nonpermissive cells.

Benson et al. report that ephrin B3 is expressed in postnatal myelinating oligodendrocytes of the central nervous system and is a constituent of purified myelin. Neurite outgrowth of postnatal cortical neurons, which express EphA4 (the receptor for ephrin B3), was inhibited when the cells were cultured in the presence of soluble ephrin B3/Fc fusion protein or a soluble fusion of the known myelin-based outgrowth inhibitor, myelin-associated glycoprotein (MAG). Indeed, the ephrin B3/Fc was more potent than MAG/Fc. Cortical neurons plated on myelin deficient for ephrin B3 showed more outgrowth compared with that of neurons whose growth was inhibited by plating on wild-type myelin. Cortical neurons deficient in p75, the receptor for several myelin-based inhibitors of neurite outgrowth, including MAG, also exhibited decreased neurite growth inhibition. However, neurite extension was restored to that of cells cultured in the absence of myelin when p75–/– neurons were plated on ephrin B3-deficient myelin. (Thus, the effects of ephrin B3 and those of the other myelin-based inhibitors appear to be additive). Inhibition of neurite outgrowth by myelin was alleviated in both cortical neurons and cerebellar granule neurons when these cells were cultured in the presence of soluble fusion proteins for EphA4 or p75. These results suggest that ephrin-Eph signaling may be another mediator of myelin-based neurite inhibition, which has implications for treatment of spinal cord injury.

M. I. Bonaparte, A. S. Dimitrov, K. N. Bossart, G. Crameri, B. A. Mungall, K. A. Bishop, V. Choudhry, D. S. Dimitrov, L.-F. Wang, B. T. Eaton, C. C. Broder, Ephrin-B2 ligand is a functional receptor for Hendra virus and Nipah virus. Proc. Natl. Acad. Sci. U.S.A. 102, 10652-10657 (2005). [Abstract] [Full Text]

M. D. Benson, M. I. Romero, M. E. Lush, Q. R. Lu, M. Henkemeyer, L. R. Parada, Ephrin-B3 is a myelin-based inhibitor of neurite outgrowth. Proc. Natl. Acad. Sci. U.S.A. 102, 10694-10699 (2005). [Abstract] [Full Text]

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