title: Malectin participates in a backup glycoprotein quality control pathway in the mammalian ER.
abstract: Malectin is a conserved, endoplasmic reticulum (ER)-resident lectin that recognizes high mannose oligosaccharides displaying terminal glucose residues. Here we show that Malectin is an ER stress-induced protein that selectively associates with glycopolypeptides without affecting their entry and their retention in the Calnexin chaperone system. Analysis of the obligate Calnexin client influenza virus hemagglutinin (HA) revealed that Calnexin and Malectin associated with different timing to different HA conformers and that Malectin associated with misfolded HA. Analysis of the facultative Calnexin clients NHK and α1-antitrypsin (α1AT) revealed that induction of Malectin expression to simulate conditions of ER stress resulted in persistent association between the ER lectin and the model cargo glycoproteins, interfered with processing of cargo-linked oligosaccharides and reduced cargo secretion. We propose that Malectin intervention is activated upon ER stress to inhibit secretion of defective gene products that might be generated under conditions of aberrant functioning of the ER quality control machinery.
authors.affiliation: Institute for Research in Biomedicine, Bellinzona, Switzerland.
authors.forename: Carmela
authors.initials: C
authors.lastname: Galli
authors.forename: Riccardo
authors.initials: R
authors.lastname: Bernasconi
authors.forename: Tatiana
authors.initials: T
authors.lastname: Soldà
authors.forename: Verena
authors.initials: V
authors.lastname: Calanca
authors.forename: Maurizio
authors.initials: M
authors.lastname: Molinari
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D037281:Calnexin; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D037102:Lectins / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D057165:Proteostasis Deficiencies / Q000517:prevention & control
chemical_list: D006023:Glycoproteins; D037102:Lectins; C554484:MLEC protein, human; D008565:Membrane Proteins; D037281:Calnexin