The interaction between F3 immunoglobulin domains and protein tyrosine phosphatases zeta/beta triggers bidirectional signalling between neurons and glial cells.
Eur J of Neuroscience. 1999-04-01; 11(4): 1134-1147
DOI: 10.1046/j.1460-9568.1999.00521.x
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AbstractF3, 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 ζ/β (PTPζ/RPTPβ) from extracts of developing mouse brain. We showed that both PTPζ/RPTPβ and tenascin‐C can bind directly to F3, possibly in an exclusive manner, with the highest affinity for the F3–PTPζ/RPTPβ 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 PTPζ/RPTPβ. We also found by confocal analysis that tenascin‐C and PTPζ/RPTPβ were colocalized on astrocytes which suggests a complex interplay of interactions between PTPζ/RPTPβ, tenascin‐C and F3. We showed that the interaction between PTPζ/RPTPβ and F3‐Ig‐like domains can trigger bidirectional signalling. C6 glia‐expressed PTPζ/RPTPβ 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 PTPζ/RPTPβ as potential mediators of a reciprocal exchange of information between glia and neurons.