The Interaction Between F3 Immunoglobulin Domains and Protein Tyrosine Phosphatases zeta/beta Triggers Bidirectional Signalling Between Neurons and Glial Cells

Eur J Neurosci. 1999 Apr;11(4):1134-47. doi: 10.1046/j.1460-9568.1999.00521.x.

Abstract

F3, a mouse glycosyl-phosphatidylinositol anchored molecule of the immunoglobulin superfamily, is known to influence axonal growth and fasciculation via multiple interactions of its modular immunoglobulin-like domains. We prepared an Fc chimeric molecule (F3IgFc) to identify molecules interacting with these domains and characterize the functional impact of the interactions. We affinity-isolated tenascin-C and isoforms of the proteoglycan-type protein tyrosine phosphatases zeta/beta (PTPzeta/RPTPbeta) from extracts of developing mouse brain. We showed that both PTPzeta/RPTPbeta and tenascin-C can bind directly to F3, possibly in an exclusive manner, with the highest affinity for the F3-PTPzeta/RPTPbeta interaction. We observed a strong binding of F3IgFc-coated fluorospheres to astrocytes in neural primary cultures and to C6 astrocytoma cells, and demonstrated, in antibody perturbation experiments, that F3-Ig binding on astrocytes depends on its interaction with PTPzeta/RPTPbeta. We also found by confocal analysis that tenascin-C and PTPzeta/RPTPbeta were colocalized on astrocytes which suggests a complex interplay of interactions between PTPzeta/RPTPbeta, tenascin-C and F3. We showed that the interaction between PTPzeta/RPTPbeta and F3-Ig-like domains can trigger bidirectional signalling. C6 glia-expressed PTPzeta/RPTPbeta stimulated neurite outgrowth by cortical and cerebellar neurons, whereas preclustered F3IgFc specifically modified the distribution of phosphotyrosine labelling in these glial cells. Both effects could be prevented and/or mimicked by anti-F3 and anti-6B4PG antibodies. These results identify F3 and PTPzeta/RPTPbeta as potential mediators of a reciprocal exchange of information between glia and neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / enzymology
  • Cell Communication / physiology
  • Cells, Cultured
  • Immunoglobulin Isotypes / chemistry*
  • Isoenzymes / chemistry*
  • Mice
  • Neuroglia / cytology*
  • Neurons / cytology*
  • Phenotype
  • Protein Structure, Tertiary*
  • Protein Tyrosine Phosphatases / chemistry*
  • Tenascin / metabolism
  • Tumor Cells, Cultured

Substances

  • Immunoglobulin Isotypes
  • Isoenzymes
  • Tenascin
  • Protein Tyrosine Phosphatases