The interaction between F3 immunoglobulin domains and protein tyrosine phosphatases zeta/beta triggers bidirectional signalling between neurons and glial cells.
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.
Revest
J M
JM
Laboratoire de Génétique et Physiologie du Développement, CNRS 6545 Parc Scientifique de Luminy, Marseille, France.
Faivre-Sarrailh
C
C
Maeda
N
N
Noda
M
M
Schachner
M
M
Rougon
G
G
D000818:Animals; D001253:Astrocytes / Q000201:enzymology; D002450:Cell Communication / Q000502:physiology; D002478:Cells, Cultured; D007132:Immunoglobulin Isotypes / Q000737:chemistry*; D007527:Isoenzymes / Q000737:chemistry*; D051379:Mice; D009457:Neuroglia / Q000166:cytology*; D009474:Neurons / Q000166:cytology*; D010641:Phenotype; D017434:Protein Structure, Tertiary; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry*; D019063:Tenascin / Q000378:metabolism; D014407:Tumor Cells, Cultured
D007132:Immunoglobulin Isotypes; D007527:Isoenzymes; D019063:Tenascin; D017027:Protein Tyrosine Phosphatases