title: Immunoglobulin heavy chain and binding protein complexes are dissociated in vivo by light chain addition.
abstract: Immunoglobulin heavy chain binding protein (BiP, GRP78) associates stably with the free, nonsecreted Ig heavy chains synthesized by Abelson virus transformed pre-B cell lines. In cells synthesizing both Ig heavy and light chains, the Ig subunits assemble rapidly and are secreted. Only incompletely assembled Ig molecules can be found bound to BiP in these cells. In addition to Ig heavy chains, a number of mutant and incompletely glycosylated transport-defective proteins are stably complexed with BiP. When normal proteins are examined for combination with BiP, only a small fraction of the intracellular pool of nascent, unfolded, or unassembled proteins can be found associated. It has been difficult to determine whether these BiP-associated molecules represent assembly intermediates which will be displaced from BiP and transported from the cell, or whether these are aberrant proteins that are ultimately degraded. In order for BiP to monitor and aid in normal protein transport, its association with these proteins must be reversible and the released proteins should be transport competent. In the studies described here, transient heterokaryons were formed between a myeloma line producing BiP-associated heavy chains and a myeloma line synthesizing the complementary light chain. Introduction of light chain synthesis resulted in assembly of prelabeled heavy chains with light chains, displacement of BiP from heavy chains, and secretion of Ig into the culture supernatant. These data demonstrate that BiP association can be reversible, with concordant release of transportable proteins. Thus, BiP can be considered a component of the exocytic secretory pathway, regulating the transport of both normal and abnormal proteins.
authors.affiliation: Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
authors.forename: L M
authors.initials: LM
authors.lastname: Hendershot
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002459:Cell Fusion; D002460:Cell Line; D000091342:Endoplasmic Reticulum Chaperone BiP; D005089:Exocytosis / Q000502:physiology*; D006360:Heat-Shock Proteins; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism*; D007147:Immunoglobulin Light Chains / Q000502:physiology*; D007136:Immunoglobulins / Q000378:metabolism; D018832:Molecular Chaperones; D011092:Polyethylene Glycols / Q000494:pharmacology; D011107:Polylysine / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007136:Immunoglobulins; D018832:Molecular Chaperones; D011107:Polylysine; D011092:Polyethylene Glycols