Document Detail


Enhanced binding to the molecular chaperone BiP slows thyroglobulin export from the endoplasmic reticulum.
MedLine Citation:
PMID:  9514162     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To examine how binding of BiP (a molecular chaperone of the hsp70 family that resides in the endoplasmic reticulum) influences the conformational maturation of thyroglobulin (Tg, the precursor for thyroid hormone synthesis), we have developed a system of recombinant Tg stably expressed in wild-type Chinese hamster ovary (CHO) cells and CHO-B cells genetically manipulated for selectively increased BiP expression. The elevation of immunoreactive BiP in CHO-B cells is comparable to that seen during the unfolded protein response in the thyrocytes of certain human patients and animals suffering from congenital hypothyroid goiter with defective Tg. However, in CHO-B cells, we expressed Tg containing no mutations that induce misfolding (i.e. no unfolded protein response), so that levels of all other endoplasmic reticulum chaperones were normal. Increased availability of BiP did not accelerate Tg secretion; rather, the export of newly synthesized Tg was delayed. Tg detained intracellularly was concentrated in the endoplasmic reticulum. By coimmunoprecipitation, BiP exhibited enhanced binding to Tg in CHO-B cells. Moreover, two-dimensional gel analysis showed that BiP associated especially well with intracellular Tg containing mispaired disulfide bonds, thought to represent early Tg folding intermediates. An endoplasmic reticulum chaperone of the hsp90 family, GRP94, was also associated in Tg-chaperone complexes. The results suggest that increased binding of BiP to Tg leads to its delayed conformational maturation in the endoplasmic reticulum.
Authors:
Z Muresan; P Arvan
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular endocrinology (Baltimore, Md.)     Volume:  12     ISSN:  0888-8809     ISO Abbreviation:  Mol. Endocrinol.     Publication Date:  1998 Mar 
Date Detail:
Created Date:  1998-05-14     Completed Date:  1998-05-14     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8801431     Medline TA:  Mol Endocrinol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  458-67     Citation Subset:  IM    
Affiliation:
Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, Massachusetts 02215, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Transport
COS Cells
Carrier Proteins / metabolism*
Cricetinae
Cross-Linking Reagents
Electrophoresis, Polyacrylamide Gel
Endoplasmic Reticulum / metabolism*
Glycosylation
Heat-Shock Proteins*
Hexosaminidases / metabolism
Immunoblotting
Microscopy, Fluorescence
Molecular Chaperones / metabolism*
Protein Folding
Recombinant Proteins / genetics,  metabolism
Thyroglobulin / chemistry,  genetics,  metabolism*
Transfection
Grant Support
ID/Acronym/Agency:
40344//PHS HHS
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Cross-Linking Reagents; 0/Heat-Shock Proteins; 0/Molecular Chaperones; 0/Recombinant Proteins; 0/molecular chaperone GRP78; 9010-34-8/Thyroglobulin; EC 3.2.1.-/Hexosaminidases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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