Thrombospondin type 1 repeat-derived ...
Document type :
Article dans une revue scientifique
Permalink :
Title :
Thrombospondin type 1 repeat-derived C-mannosylated peptide attenuates synaptogenesis of cortical neurons induced by primary astrocytes via TGF-β
Author(s) :
Nishitsuji, Kazuchika [Auteur]
Wakayama University
Ikezaki, Midori [Auteur]
Wakayama University
Manabe, Shino [Auteur]
Hoshi University [Tokyo]
Uchimura, Kenji [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Ito, Yukishige [Auteur]
Osaka University
Ihara, Yoshito [Auteur]
Wakayama University
Wakayama University
Ikezaki, Midori [Auteur]
Wakayama University
Manabe, Shino [Auteur]
Hoshi University [Tokyo]
Uchimura, Kenji [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Ito, Yukishige [Auteur]
Osaka University
Ihara, Yoshito [Auteur]
Wakayama University
Journal title :
Glycoconjugate journal
Abbreviated title :
Glycoconj J
Volume number :
2021
Publisher :
Springer Science and Business Media LLC
Publication date :
2021-11-18
ISSN :
1573-4986
English keyword(s) :
C-Mannosylation
TGF-β
Synaptogenesis
Astrocyte
Neuron
TGF-β
Synaptogenesis
Astrocyte
Neuron
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
C-Mannosylation is a rare type of protein glycosylation and is reportedly critical for the proper folding and secretion of parental proteins. Still, the effects of C-mannosylation on the biological functions of these ...
Show more >C-Mannosylation is a rare type of protein glycosylation and is reportedly critical for the proper folding and secretion of parental proteins. Still, the effects of C-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 be C-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 whether C-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 the C-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 the C-Man-WSPW peptide were similar to those with non-C-mannosylated WSPW peptide. Taken together, our results reveal a novel function of C-mannosylation of the WxxW motif in signaling and synaptogenesis mediated by TGF-β. Molecular details of how C-mannosylation affects the biological functions of WxxW motifs deserve future study for clarification.Show less >
Show more >C-Mannosylation is a rare type of protein glycosylation and is reportedly critical for the proper folding and secretion of parental proteins. Still, the effects of C-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 be C-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 whether C-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 the C-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 the C-Man-WSPW peptide were similar to those with non-C-mannosylated WSPW peptide. Taken together, our results reveal a novel function of C-mannosylation of the WxxW motif in signaling and synaptogenesis mediated by TGF-β. Molecular details of how C-mannosylation affects the biological functions of WxxW motifs deserve future study for clarification.Show less >
Language :
Anglais
Peer reviewed article :
Oui
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
Université de Lille
CNRS
CNRS
Research team(s) :
Diversité structurale des héparanes sulfates et régulation de la réponse inflammatoire
Submission date :
2022-01-11T11:37:51Z
2022-01-12T10:14:51Z
2022-01-12T10:14:51Z
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