GM1 structural requirements to mediate neuronal functions.

Autor: Fazzari M; Department of Medical Biotechnology and Translational Medicine, University of Milano, Segrate, Milano, Italy., Lunghi G; Department of Medical Biotechnology and Translational Medicine, University of Milano, Segrate, Milano, Italy., Di Biase E; Department of Medical Biotechnology and Translational Medicine, University of Milano, Segrate, Milano, Italy., Maggioni M; Department of Medical Biotechnology and Translational Medicine, University of Milano, Segrate, Milano, Italy., Carsana EV; Department of Medical Biotechnology and Translational Medicine, University of Milano, Segrate, Milano, Italy., Cioccarelli L; Department of Medical Biotechnology and Translational Medicine, University of Milano, Segrate, Milano, Italy., Vigani L; Department of Medical Biotechnology and Translational Medicine, University of Milano, Segrate, Milano, Italy., Loberto N; Department of Medical Biotechnology and Translational Medicine, University of Milano, Segrate, Milano, Italy., Aureli M; Department of Medical Biotechnology and Translational Medicine, University of Milano, Segrate, Milano, Italy., Mauri L; Department of Medical Biotechnology and Translational Medicine, University of Milano, Segrate, Milano, Italy., Ciampa MG; Department of Medical Biotechnology and Translational Medicine, University of Milano, Segrate, Milano, Italy., Valsecchi M; Department of Medical Biotechnology and Translational Medicine, University of Milano, Segrate, Milano, Italy., Takato K; Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan., Imamura A; Department of Applied Bioorganic Chemistry, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan.; Institute for Glyco-core Research (iGCORE), Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan., Ishida H; Department of Applied Bioorganic Chemistry, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan.; Institute for Glyco-core Research (iGCORE), Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan., Ben Mariem O; Dipartimento di Scienze Farmacologiche e Biomolecolari 'Rodolfo Paoletti', Università degli Studi di Milano, Milano, Italy., Saporiti S; Analytical Excellence & Program Management, Merck Serono S.p.A, Rome, Italy., Palazzolo L; Dipartimento di Scienze Farmacologiche e Biomolecolari 'Rodolfo Paoletti', Università degli Studi di Milano, Milano, Italy., Chiricozzi E; Department of Medical Biotechnology and Translational Medicine, University of Milano, Segrate, Milano, Italy. elena.chiricozzi@unimi.it., Eberini I; Dipartimento di Scienze Farmacologiche e Biomolecolari 'Rodolfo Paoletti', Università degli Studi di Milano, Milano, Italy.; Data Science Research Center, Università degli Studi di Milano, Milano, Italy., Sonnino S; Department of Medical Biotechnology and Translational Medicine, University of Milano, Segrate, Milano, Italy. sandro.sonnino@unimi.it.
Jazyk: angličtina
Zdroj: Glycoconjugate journal [Glycoconj J] 2023 Dec; Vol. 40 (6), pp. 655-668. Date of Electronic Publication: 2023 Dec 15.
DOI: 10.1007/s10719-023-10141-8
Abstrakt: Since the 1980s, it has been known that the administration of ganglioside GM1 to cultured cells induced or enhanced neuronal differentiation. GM1 mechanism of action relies on its direct interaction and subsequent activation of the membrane tyrosine kinase receptor, TrkA, which naturally serves as NGF receptor. This process is mediated by the sole oligosaccharide portion of GM1, the pentasaccharide β-Gal-(1-3)-β-GalNAc-(1-4)-[α-Neu5Ac-(2-3)]-β-Gal-(1-4)-β-Glc. Here we detailed the minimum structural requirements of the oligosaccharide portion of GM1 for mediating the TrkA dependent neuritogenic processing. By in vitro and in silico biochemical approaches, we demonstrated that the minimal portion of GM1 required for the TrkA activation is the inner core of the ganglioside's oligosaccharide β-Gal-(1-3)-β-GalNAc-(1-4)-[α-Neu5Ac-(2-3)]-β-Gal. The addition of a sialic acid residue at position 3 of the outer galactose of the GM1 oligosaccharide, which forms the oligosaccharide of GD1a, prevented the interaction with TrkA and the resulting neuritogenesis. On the contrary, the addition of a fucose residue at position 2 of the outer galactose, forming the Fucosyl-GM1 oligosaccharide, did not prevent the TrkA-mediated neuritogenesis.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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