title: LMAN1 (ERGIC-53) is a potential carrier protein for matrix metalloproteinase-9 glycoprotein secretion.
abstract: Matrix metalloproteinase-9 (MMP-9) is a secreted glycoprotein with a major role in shaping the extracellular matrix and a detailed understanding of the secretory mechanism could help identify methods to correct diseases resulting from dysregulation of secretion. MMP-9 appears to follow a canonical secretory pathway through a quality control cycle in the endoplasmic reticulum (ER) before transport of the properly folded protein to the Golgi apparatus and beyond for secretion. Through a complementation assay, we determined that LMAN1, a well-studied lectin-carrier protein, interacts with a secretion-competent N-glycosylated MMP-9 in the ER while N-glycosylation-deficient secretion-compromised MMP-9 does not. In contrast, co-immunoprecipitation demonstrated protein interaction between LMAN1 and secretion-compromised N-glycosylation-deficient MMP-9. MMP-9 secretion was reduced in the LMAN1 knockout cell line compared to control cells confirming the functional role of LMAN1. These observations support the role of LMAN1 as a lectin-carrier protein mediating efficient MMP-9 secretion.
authors.affiliation: Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA.
authors.forename: Tyler
authors.initials: T
authors.lastname: Duellman
authors.affiliation: Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA.
authors.forename: John
authors.initials: J
authors.lastname: Burnett
authors.affiliation: Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA.
authors.forename: Alice
authors.initials: A
authors.lastname: Shin
authors.affiliation: Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA. Electronic address: Jyang75@wisc.edu.
authors.forename: Jay
authors.initials: J
authors.lastname: Yang
mesh_terms: D019943:Amino Acid Substitution; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002738:Chloroquine / Q000494:pharmacology; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D004721:Endoplasmic Reticulum / Q000378:metabolism; D055786:Gene Knockout Techniques; D005816:Genetic Complementation Test; D006031:Glycosylation; D057809:HEK293 Cells; D006801:Humans; D008164:Luminescent Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D037241:Mannose-Binding Lectins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D054730:Protein Interaction Domains and Motifs; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; C084004:LMAN1 protein, human; D008164:Luminescent Proteins; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; C054562:yellow fluorescent protein, Bacteria; D002738:Chloroquine; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Glycoprotein; Lectin-carrier protein; Matrix metalloproteinase-9; Secretion