Fiche publication
Date publication
décembre 2016
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BLAISE Sébastien
,
Pr DAUCHEZ Manuel
,
Pr DEBELLE Laurent
,
Dr DUCA Laurent
,
Pr MARTINY Laurent
,
Pr BAUD Stéphanie
Tous les auteurs :
Maurice P, Baud S, Bocharova OV, Bocharov EV, Kuznetsov AS, Kawecki C, Bocquet O, Romier B, Gorisse L, Ghirardi M, Duca L, Blaise S, Martiny L, Dauchez M, Efremov RG, Debelle L
Lien Pubmed
Résumé
Neuraminidase 1 (NEU1) is a lysosomal sialidase catalyzing the removal of terminal sialic acids from sialyloconjugates. A plasma membrane-bound NEU1 modulating a plethora of receptors by desialylation, has been consistently documented from the last ten years. Despite a growing interest of the scientific community to NEU1, its membrane organization is not understood and current structural and biochemical data cannot account for such membrane localization. By combining molecular biology and biochemical analyses with structural biophysics and computational approaches, we identified here two regions in human NEU1 - segments 139-159 (TM1) and 316-333 (TM2) - as potential transmembrane (TM) domains. In membrane mimicking environments, the corresponding peptides form stable α-helices and TM2 is suited for self-association. This was confirmed with full-size NEU1 by co-immunoprecipitations from membrane preparations and split-ubiquitin yeast two hybrids. The TM2 region was shown to be critical for dimerization since introduction of point mutations within TM2 leads to disruption of NEU1 dimerization and decrease of sialidase activity in membrane. In conclusion, these results bring new insights in the molecular organization of membrane-bound NEU1 and demonstrate, for the first time, the presence of two potential TM domains that may anchor NEU1 in the membrane, control its dimerization and sialidase activity.
Référence
Sci Rep. 2016 Dec;6:38363
