NEU3 Sialidase Protein Interactors in the Plasma Membrane and in the Endosomes

• Published in: The Journal of biological chemistry Vol. 291; no. 20; pp. 10615 - 10624
• Main Authors: Cirillo, Federica, Ghiroldi, Andrea, Fania, Chiara, Piccoli, Marco, Torretta, Enrica, Tettamanti, Guido, Gelfi, Cecilia, Anastasia, Luigi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13-05-2016; American Society for Biochemistry and Molecular Biology
• Subjects: Cell Membrane - enzymology; endosome; endosomes; Endosomes - enzymology; ganglioside; gangliosides; Glycobiology and Extracellular Matrices; Heat-Shock Proteins - metabolism; HEK293 Cells; HeLa Cells; Humans; NEU3; Neuraminidase - chemistry; Neuraminidase - genetics; Neuraminidase - metabolism; Protein Folding; Protein Transport; protein-protein interaction; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; sialidase; sphingolipid; Stress, Physiological; Up-Regulation; sialidase; NEU3; endosome; sphingolipid; gangliosides; endosomes; protein-protein interaction; ganglioside
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M116.719518

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.