Hormonal regulation of thyroglobulin export from the endoplasmic reticulum of cultured thyrocytes.
To understand how the endoplasmic reticulum (ER) of the thyrocyte remains flexible to physiologic changes in the load of exportable proteins, we have examined hormonally-induced increments in thyroglobulin (Tg) flux and pool size in the ER, the relationship between kinetics of Tg folding and ER export, and steady-state levels of molecular chaperones. Tg production was increased > or = 5-fold by chronic exposure to thyrotropin (TSH), and > or = 25-fold by exposure to a mixture of TSH, insulin, transferrin, and hydrocortisone (4H). In TSH-grown cells Tg assembly was accelerated, specifically involving early folding intermediates that lead to a compact monomer. Accelerated dissociation of nascent Tg from the binding protein, BiP, was observed in parallel. TSH exposure was accompanied by modest increases in ER chaperones as well as accelerated Tg export from the thyrocyte ER. However, in 4H-grown thyrocytes, although there were further increases in ER chaperones, monomer maturation was slowed and the association between nascent Tg and BiP was prolonged. Nevertheless, export from the ER remained accelerated, indicating that exit from the ER must include other regulated steps that occur after the folding of exportable proteins. Thus, protein folding may not necessarily be the rate-limiting step in the export of newly synthesized proteins from the ER.
Kim
P S
PS
Division of Endocrinology, Beth Israel Hospital, Boston, Massachusetts.
Arvan
P
P
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D018833:Chaperonins; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D006728:Hormones / Q000502:physiology*; D008969:Molecular Sequence Data; D017510:Protein Folding; D011506:Proteins; D013552:Swine; D013954:Thyroglobulin / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism*
D006728:Hormones; D011506:Proteins; D013954:Thyroglobulin; D018833:Chaperonins