Translocational pausing of apolipoprotein B can be regulated by membrane lipid composition

One potential mechanism by which apolipoprotein (apo) B secretion is regulated is via transient pausing during translocation across the endoplasmic reticulum membrane. We have previously shown that translocation and secretion of full-length and truncated variants of apoB 100 are impaired in hepatocy...

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Bibliographic Details
Published in:Journal of lipid research 1998-06, Vol.39 (6), p.1287-1294
Main Authors: Rusiñol, A E, Hegde, R S, Chuck, S L, Lingappa, V R, Vance, J E
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
apolipoprotein B
Apolipoproteins B - biosynthesis
Apolipoproteins B - metabolism
Humans
Intracellular Membranes - metabolism
Male
Membrane Lipids - physiology
Microsomes, Liver - metabolism
Molecular Sequence Data
Phosphatidylethanolamines - physiology
phosphatidylmonomethylethanolamine
Protein Biosynthesis
Proto-Oncogene Proteins c-myc - biosynthesis
Rabbits
Rats
Rats, Sprague-Dawley
Recombinant Fusion Proteins - biosynthesis
secretion
Transcription, Genetic
translocation
translocational pausing
VLDL
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Summary:One potential mechanism by which apolipoprotein (apo) B secretion is regulated is via transient pausing during translocation across the endoplasmic reticulum membrane. We have previously shown that translocation and secretion of full-length and truncated variants of apoB 100 are impaired in hepatocytes in which microsomal membranes are enriched in the phospholipid phosphatidylmonomethylethanolamine (PMME). We have now investigated whether or not the decreased translocation of apoB is the result of altered membrane lipid composition having an impact on translocational pausing. Our experiments showed that less in vitro translated apoB-15 (the N-terminal 15% of human apoB-100) was translocated into the lumen of PMME-enriched microsomes than of control microsomes. Proteinase K treatment of the translocation products yielded discrete N-terminal fragments of apoB indicating that both types of microsomal membranes contained translocationally paused nascent chains. Similarly, apoB generated from a truncated mRNA lacking a stop codon was also found to be translocationally paused. However, restarting of translocation after translocational pausing was impaired in PMME-enriched, but not in control, microsomes. These data suggest that secretion of apoB-containing lipoproteins can be regulated by membrane lipid composition at the level of translocational pausing.
ISSN:0022-2275
DOI:10.1016/S0022-2275(20)32554-2