MacDonald, EwanEwanMacDonaldForrester, AlisonAlisonForresterValades-Cruz, Cesar A.Cesar A.Valades-CruzMadsen, Thomas D.Thomas D.MadsenHetmanski, Joseph H.R.Joseph H.R.HetmanskiDransart, EstelleEstelleDransartNg, YeapYeapNgGodbole, RashmiRashmiGodboleShp, Ananthan AkhilAnanthan AkhilShpLeconte, LudovicLudovicLeconteChambon, ValérieValérieChambonGhosh, DebarpanDebarpanGhoshPinet, AlexisAlexisPinetBhatia, DhirajDhirajBhatiaLombard, BérangèreBérangèreLombardLoew, DamarysDamarysLoewLarsen, Martin R.Martin R.LarsenLeffler, HakonHakonLefflerLefeber, Dirk J.Dirk J.LefeberClausen, HenrikHenrikClausenBlangy, AnneAnneBlangyCaswell, PatrickPatrickCaswellShafaq-Zadah, MassiullahMassiullahShafaq-ZadahMayor, SatyajitSatyajitMayorWeigert, RobertoRobertoWeigertWunder, ChristianChristianWunderJohannes, LudgerLudgerJohannes2025-08-312025-08-312025-03-0110.1038/s41556-025-01616-x2-s2.0-85218711814http://repository.iitgn.ac.in/handle/IITG2025/2824940000851Glycolipid-lectin-driven endocytosis controls the formation of clathrin-independent carriers and the internalization of various cargos such as β1 integrin. Whether this process is regulated in a dynamic manner remained unexplored. Here we demonstrate that, within minutes, the epidermal growth factor triggers the galectin-driven endocytosis of cell-surface glycoproteins, such as integrins, that are key regulators of cell adhesion and migration. The onset of this process—mediated by the Na⁺/H⁺ antiporter NHE1 as well as the neuraminidases Neu1 and Neu3—requires the pH-triggered enzymatic removal of sialic acids whose presence otherwise prevents galectin binding. De-sialylated glycoproteins are then retrogradely transported to the Golgi apparatus where their glycan make-up is reset to regulate EGF-dependent invasive-cell migration. Further evidence is provided for a role of neuraminidases and galectin-3 in acidification-dependent bone resorption. Glycosylation at the cell surface thereby emerges as a dynamic and reversible regulatory post-translational modification that controls a highly adaptable trafficking pathway.falseArticle14764679449-463March 202541457arJournal4WOS:001427394900001