title: NEU3 Sialidase Protein Interactors in the Plasma Membrane and in the Endosomes.
abstract: NEU3 sialidase has been shown to be a key player in many physio- and pathological processes, including cell differentiation, cellular response to hypoxic stress, and carcinogenesis. The enzyme, peculiarly localized on the outer leaflet of the plasma membrane, has been shown to be able to remove sialic acid residues from the gangliosides present on adjacent cells, thus creating cell to cell interactions. Nonetheless, herein we report that the enzyme localization is dynamically regulated between the plasma membrane and the endosomes, where a substantial amount of NEU3 is stored with low enzymatic activity. However, under opportune stimuli, NEU3 is shifted from the endosomes to the plasma membrane, where it greatly increases the sialidase activity. Finally, we found that NEU3 possesses also the ability to interact with specific proteins, many of which are different in each cell compartment. They were identified by mass spectrometry, and some selected ones were also confirmed by cross-immunoprecipitation with the enzyme, supporting NEU3 involvement in the cell stress response, protein folding, and intracellular trafficking.
authors.affiliation: From the Istituto Di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, 20097 San Donato Milanese, Milan and.
authors.forename: Federica
authors.initials: F
authors.lastname: Cirillo
authors.affiliation: From the Istituto Di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, 20097 San Donato Milanese, Milan and.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ghiroldi
authors.affiliation: From the Istituto Di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, 20097 San Donato Milanese, Milan and.
authors.forename: Chiara
authors.initials: C
authors.lastname: Fania
authors.affiliation: From the Istituto Di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, 20097 San Donato Milanese, Milan and.
authors.forename: Marco
authors.initials: M
authors.lastname: Piccoli
authors.affiliation: the Department of Biomedical Sciences for Health, University of Milan, 20122 Milan, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Torretta
authors.affiliation: From the Istituto Di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, 20097 San Donato Milanese, Milan and.
authors.forename: Guido
authors.initials: G
authors.lastname: Tettamanti
authors.affiliation: From the Istituto Di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, 20097 San Donato Milanese, Milan and the Department of Biomedical Sciences for Health, University of Milan, 20122 Milan, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Gelfi
authors.affiliation: From the Istituto Di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, 20097 San Donato Milanese, Milan and the Department of Biomedical Sciences for Health, University of Milan, 20122 Milan, Italy luigi.anastasia@unimi.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Anastasia
mesh_terms: D002462:Cell Membrane / Q000201:enzymology; D000091342:Endoplasmic Reticulum Chaperone BiP; D011992:Endosomes / Q000201:enzymology; D057809:HEK293 Cells; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D009439:Neuraminidase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017510:Protein Folding; D021381:Protein Transport; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological; D015854:Up-Regulation
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D011994:Recombinant Proteins; C465436:Neu3 protein, human; D009439:Neuraminidase
keywords: NEU3; endosome; endosomes; ganglioside; gangliosides; protein-protein interaction; sialidase; sphingolipid