title: The role of MTJ-1 in cell surface translocation of GRP78, a receptor for alpha 2-macroglobulin-dependent signaling.
abstract: MTJ-1 associates with a glucose-regulated protein of Mr approximately 78,000(GRP78) in the endoplasmic reticulum and modulates GRP78 activity as a chaperone. GRP78 also exists on the cell surface membrane, where it is associated with a number of functions. MHC class I Ags on the cell surface are complexed to GRP78. GRP78 also serves as the receptor for alpha2-macroglobulin-dependent signaling and for uptake of certain pathogenic viruses. The means by which GRP78, lacking a transmembrane domain, can fulfill such functions is unclear. In this study we have examined the question of whether MTJ-1, a transmembrane protein, is involved in the translocation of GRP78 to the cell surface. MTJ-1 and GRP78 coimmunoprecipitated from macrophage plasma membrane lysates. Silencing of MTJ-1 gene expression greatly reduced MTJ-1 mRNA and protein levels, but also abolished cell surface localization of GRP78. Consequently, binding of the activated and receptor-recognized form of alpha2-macroglobulin to macrophages was greatly reduced, and activated and receptor-recognized form of alpha2-macroglobulin-induced calcium signaling was abolished in these cells. In conclusion, we show that in addition to assisting the chaperone GRP78 in protein quality control in the endoplasmic reticulum, MTJ-1 is essential for transport of GRP78 to the cell surface, which serves a number of functions in immune regulation and signal transduction.
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Uma Kant
authors.initials: UK
authors.lastname: Misra
authors.forename: Mario
authors.initials: M
authors.lastname: Gonzalez-Gronow
authors.forename: Govind
authors.initials: G
authors.lastname: Gawdi
authors.forename: Salvatore Vincent
authors.initials: SV
authors.lastname: Pizzo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020013:Calcium Signaling / Q000235:genetics / Q000276:immunology; D002458:Cell Fractionation; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D000091342:Endoplasmic Reticulum Chaperone BiP; D020868:Gene Silencing; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D047468:Immunoprecipitation; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism* / Q000502:physiology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018832:Molecular Chaperones / Q000378:metabolism* / Q000502:physiology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding; D021381:Protein Transport / Q000235:genetics / Q000276:immunology; D034622:RNA Interference; D011971:Receptors, Immunologic / Q000378:metabolism* / Q000502:physiology; D014162:Transfection
chemical_list: C092319:Dnajc1 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D011971:Receptors, Immunologic