title: NEU1 sialidase expressed in human airway epithelia regulates epidermal growth factor receptor (EGFR) and MUC1 protein signaling.
abstract: Epithelial cells (ECs) lining the airways provide a protective barrier between the external environment and the internal host milieu. These same airway epithelia express receptors that respond to danger signals and initiate repair programs. Because the sialylation state of a receptor can influence its function and is dictated in part by sialidase activity, we asked whether airway epithelia express catalytically active sialidase(s). Human primary small airway and A549 ECs expressed NEU1 sialidase at the mRNA and protein levels, and NEU1 accounted for >70% of EC sialidase activity. Blotting with Maackia amurensis and peanut agglutinin lectins established epidermal growth factor receptor (EGFR) and MUC1 as in vivo substrates for NEU1. NEU1 associated with EGFR and MUC1, and NEU1-EGFR association was regulated by EGF stimulation. NEU1 overexpression diminished EGF-stimulated EGFR Tyr-1068 autophosphorylation by up to 44% but enhanced MUC1-dependent Pseudomonas aeruginosa adhesion by 1.6-1.7-fold and flagellin-stimulated ERK1/2 activation by 1.7-1.9-fold. In contrast, NEU1 depletion increased EGFR activation (1.5-fold) and diminished MUC1-mediated bacterial adhesion (38-56%) and signaling (73%). These data indicate for the first time that human airway epithelia express catalytically active NEU1 sialidase that regulates EGFR- and MUC1-dependent signaling and bacterial adhesion. NEU1 catalytic activity may offer an additional level of regulation over the airway epithelial response to ligands, pathogens, and injurious stimuli.
authors.affiliation: Departments of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Erik P
authors.initials: EP
authors.lastname: Lillehoj
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Hyun
authors.forename: Chiguang
authors.initials: C
authors.lastname: Feng
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Anguo
authors.initials: A
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Guang
authors.forename: Chinh
authors.initials: C
authors.lastname: Nguyen
authors.forename: Irina G
authors.initials: IG
authors.lastname: Luzina
authors.forename: Sergei P
authors.initials: SP
authors.lastname: Atamas
authors.forename: Antonino
authors.initials: A
authors.lastname: Passaniti
authors.forename: William S
authors.initials: WS
authors.lastname: Twaddell
authors.forename: Adam C
authors.initials: AC
authors.lastname: Puché
authors.forename: Lai-Xi
authors.initials: LX
authors.lastname: Wang
authors.forename: Alan S
authors.initials: AS
authors.lastname: Cross
authors.forename: Simeon E
authors.initials: SE
authors.lastname: Goldblum
mesh_terms: D002461:Cell Line, Transformed; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism*; D009439:Neuraminidase / Q000096:biosynthesis* / Q000235:genetics; D011552:Pseudomonas Infections / Q000235:genetics / Q000378:metabolism / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000378:metabolism; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000382:microbiology
chemical_list: C060192:MUC1 protein, human; D018396:Mucin-1; D004815:Epidermal Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C486385:NEU1 protein, human; D009439:Neuraminidase