title: The polypeptide binding conformation of calreticulin facilitates its cell-surface expression under conditions of endoplasmic reticulum stress.
abstract: We define two classes of calreticulin mutants that retain glycan binding activity; those that display enhanced or reduced polypeptide-specific chaperone activity, due to conformational effects. Under normal conditions, neither set of mutants significantly impacts the ability of calreticulin to mediate assembly and trafficking of major histocompatibility complex class I molecules, which are calreticulin substrates. However, in cells treated with thapsigargin, which depletes endoplasmic reticulum calcium, major histocompatibility complex class I trafficking rates are accelerated coincident with calreticulin secretion, and detection of cell-surface calreticulin is dependent on its polypeptide binding conformations. Together, these findings identify a site on calreticulin that is an important determinant of the induction of its polypeptide binding conformation and demonstrate the relevance of the polypeptide binding conformations of calreticulin to endoplasmic reticulum stress-induced interactions.
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Elise
authors.initials: E
authors.lastname: Jeffery
authors.forename: Larry Robert
authors.initials: LR
authors.lastname: Peters
authors.forename: Malini
authors.initials: M
authors.lastname: Raghavan
mesh_terms: D000818:Animals; D064032:Calbindin 2; D002118:Calcium / Q000378:metabolism; D020134:Catalytic Domain / Q000235:genetics; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D018832:Molecular Chaperones / Q000096:biosynthesis* / Q000235:genetics; D009154:Mutation; D010449:Peptide Mapping; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics; D064030:S100 Calcium Binding Protein G / Q000096:biosynthesis* / Q000235:genetics; D013312:Stress, Physiological; D019284:Thapsigargin / Q000494:pharmacology; D056811:Unfolded Protein Response
chemical_list: D064032:Calbindin 2; D004791:Enzyme Inhibitors; D015395:Histocompatibility Antigens Class I; D018832:Molecular Chaperones; D064030:S100 Calcium Binding Protein G; D019284:Thapsigargin; D002118:Calcium