Thrombospondin type 1 repeat-derived C-mannosylated peptide attenuates synaptogenesis of cortical neurons induced by primary astrocytes via TGF- β

AbstractC-Mannosylation is a rare type of protein glycosylation and is reportedly critical for the proper folding and secretion of parental proteins. Still, the effects ofC-mannosylation on the biological functions of these modified proteins remain to be elucidated. The Trp-x-x-Trp (WxxW) sequences, whose first tryptophan (Trp) can beC-mannosylated, constitute the consensus motifs for this glycosylation modification and are commonly found in thrombospondin type 1 repeats that regulate molecular functions of thrombospondin 1 in binding and activation of transforming growth factor β (TGF-β). TGF-β plays critical roles in the control of the central nervous system including synaptogenesis. Here, we investigated whetherC-mannosylation of the synthetic Trp-Ser-Pro-Trp (WSPW) peptide may confer certain functions to this peptide in TGF- β-mediated synaptogenesis. By using primary cultured rat astrocytes and cortical neurons, we found that theC-mannosylated WSPW (C-Man-WSPW) peptide, but not non-mannosylated WSPW peptide, suppressed astrocyte-conditioned medium (ACM)-stimulated synaptogenesis.C-Man-WSPW peptide inhibited both ACM- and recombinant mature TGF- β1-induced activations of Smad 2, an important mediator in TGF-β signaling. Interactions of recombinant mature TGF-β with theC-Man-WSPW peptide were similar to those with non-C-mannosylated WSPW peptide. Taken together, our results reveal a novel function ofC-mannosylation of the WxxW motif in signaling and synaptogenesis m...
Source: Glycoconjugate Journal - Category: Biochemistry Source Type: research