Biosynthesis of the IgA antibody receptor: a model for the transepithelial sorting of a membrane glycoprotein.
Secretory IgA dimer antibodies in exosecretions provide the primary immunological defense for mucosal surfaces. Transmission of IgA2 across the epithelia of mucous and exocrine glands is mediated by a receptor called secretory component (SC). Using three antibodies directed against different domains of SC, we examine its processing in the lactating rabbit mammary gland. SC is synthesized as a core glycosylated transmembrane glycoprotein on the rough endoplasmic reticulum. Pulse-chase experiments reveal the time course of SC maturation in the Golgi, as demonstrated by the acquisition of Endo H resistance (30-60 min). The subsequent routing of SC to the basolateral plasma membrane, where IgA2 binding and endocytosis occurs, the cleavage of the membrane anchoring domain of SC, and the exocytosis from the apical plasma membrane of IgA, bound to the ectoplasmic domain of SC takes place rapidly (30-60 min). Thus maturation in the Golgi may represent the rate limiting step in SC routing. We also demonstrate that SC exists in several conformational states that are processed at different rates.
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005260:Female; D006026:Glycoside Hydrolases / Q000494:pharmacology; D006056:Golgi Apparatus / Q000378:metabolism; D007071:Immunoglobulin A, Secretory / Q000378:metabolism*; D007128:Immunoglobulin Fragments / Q000096:biosynthesis*; D007700:Kinetics; D007774:Lactation; D008321:Mammary Glands, Animal / Q000378:metabolism*; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase; D008970:Molecular Weight; D011247:Pregnancy; D011499:Protein Processing, Post-Translational; D011817:Rabbits; D012635:Secretory Component / Q000096:biosynthesis*
D007071:Immunoglobulin A, Secretory; D007128:Immunoglobulin Fragments; D012635:Secretory Component; D006026:Glycoside Hydrolases; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase