Document Detail


Acquisition of Lubrol insolubility, a common step for growth hormone and prolactin in the secretory pathway of neuroendocrine cells.
MedLine Citation:
PMID:  11024038     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Rat prolactin in the dense cores of secretory granules of the pituitary gland is a Lubrol-insoluble aggregate. In GH(4)C(1) cells, newly synthesized rat prolactin and growth hormone were soluble, but after 30 min about 40% converted to a Lubrol-insoluble form. Transport from the endoplasmic reticulum is necessary for conversion to Lubrol insolubility, since incubating cells with brefeldin A or at 15 degrees C reduced formation of insoluble rat (35)S-prolactin. Formation of Lubrol-insoluble aggregates has protein and cell specificity; newly synthesized human growth hormone expressed in AtT20 cells underwent a 40% conversion to Lubrol insolubility with time, but albumin did not, and human growth hormone expressed in COS cells underwent less than 10% conversion to Lubrol insolubility. del32-46 growth hormone, a naturally occurring form of growth hormone, and P89L growth hormone underwent conversion, although they were secreted more slowly, indicating that there is some tolerance in structural requirements for aggregation. An intracellular compartment with an acidic pH is not necessary for conversion to Lubrol insolubility, because incubation with chloroquine or bafilomycin slowed, but did not prevent, the conversion. GH(4)C(1) cells treated with estradiol, insulin, and epidermal growth factor accumulate more secretory granules and store more prolactin, but not more growth hormone, than untreated cells; Lubrol-insoluble aggregates of prolactin and growth hormone formed to the same extent in hormone-treated or untreated GH(4)C(1) cells, but prolactin was retained longer in hormone-treated cells. These findings indicate that aggregation alone is not sufficient to cause retention of secretory granule proteins, and there is an additional selective process.
Authors:
M S Lee; Y L Zhu; J E Chang; P S Dannies
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  276     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2001 Jan 
Date Detail:
Created Date:  2001-02-08     Completed Date:  2001-02-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  715-21     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Bacterial Agents / pharmacology
Brefeldin A / pharmacology
COS Cells
Chloroquine / pharmacology
Dinitrobenzenes / pharmacology
Endoplasmic Reticulum / chemistry,  drug effects,  metabolism,  secretion
Epidermal Growth Factor / pharmacology
Estradiol / pharmacology
Human Growth Hormone / chemistry,  genetics,  metabolism*,  secretion
Hydrogen-Ion Concentration
Insulin / pharmacology
Macrolides*
Mutation
Pituitary Gland / cytology,  drug effects,  metabolism,  secretion*
Polyethylene Glycols / pharmacology*
Prolactin / chemistry,  genetics,  metabolism*,  secretion
Protein Transport / drug effects
Rats
Secretory Vesicles / chemistry,  drug effects,  metabolism,  secretion*
Solubility / drug effects
Substrate Specificity
Tumor Cells, Cultured
Ultracentrifugation
Grant Support
ID/Acronym/Agency:
DK 46807/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Dinitrobenzenes; 0/Macrolides; 0/Polyethylene Glycols; 11061-68-0/Insulin; 116764-51-3/bafilomycin A; 12629-01-5/Human Growth Hormone; 20350-15-6/Brefeldin A; 50-28-2/Estradiol; 52434-01-2/lubrol; 54-05-7/Chloroquine; 62229-50-9/Epidermal Growth Factor; 9002-62-4/Prolactin; 92585-03-0/3-(2,4-dinitroanilino)-3'-amino-N-methyldipropylamine

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


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