Signals for retention of transmembrane proteins in the endoplasmic reticulum studied with CD4 truncation mutants.
- 1 March 1991
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 88 (5), 1918-1922
- https://doi.org/10.1073/pnas.88.5.1918
Abstract
A mutant of CD4 (CD4.Q421stop), in which the cytoplasmic C-terminal 13 amino acids were truncated, was not expressed on the surface of HeLa cells after transfection but was retained in the endoplasmic reticulum (ER). Seven other truncation mutants of CD4 were expressed well on the cell surface, thus suggesting that the C-terminal amino acids of CD4.Q421stop (-Ser-Glu-Lys-Lys-Thr-Cys) may have the sequence information for ER retention. Further mutational study has revealed that two consecutive lysine residues at the third and fourth positions from the C-terminal end are sufficient for ER retention. Lysine at the fourth position, but not at the third position, from the C terminus can be replaced by arginine without disturbing ER retention. Furthermore, two lysine residues at the third and fifth positions from the C terminus also resulted in ER retention. Thus lysine at the third position and a positively charged amino acid either at the fourth or fifth position from the C terminus are sufficient for ER retention of this CD4 mutant, and possibly all transmembrane proteins. In addition to the requirement of specific amino acids at specific positions, the ER retention signal -Lys-Lys-Xaa-Xaa also requires a transmembrane region for function. By contrast -Lys-Asp-Glu-Leu, which targets soluble proteins to the lumen of the ER, does not function in the presence of a transmembrane region.This publication has 15 references indexed in Scilit:
- A human homologue of the yeast HDEL receptorNature, 1990
- Short cytoplasmic sequences serve as retention signals for transmembrane proteins in the endoplasmic reticulumCell, 1989
- Molecular Cloning and Expression of cDNA Encoding the 53,000-Dalton Glycoprotein of Rabbit Skeletal Muscle Sarcoplasmic ReticulumOnline Journal of Public Health Informatics, 1989
- Transport of secretory and membrane glycoproteins from the rough endoplasmic reticulum to the Golgi. A rate-limiting step in protein maturation and secretion.Online Journal of Public Health Informatics, 1988
- Assembly of the human T cell receptor-CD3 complex takes place in the endoplasmic reticulum and involves intermediary complexes between the CD3-gamma.delta.epsilon core and single T cell receptor alpha or beta chains.Online Journal of Public Health Informatics, 1988
- Failure to synthesize the T Cell CD3-? chain: Structure and function of a partial T cell receptor complexCell, 1988
- High-efficiency transformation of mammalian cells by plasmid DNA.Molecular and Cellular Biology, 1987
- A C-terminal signal prevents secretion of luminal ER proteinsCell, 1987
- Human 3-hydroxy-3-methylglutaryl coenzyme A reductase. Conserved domains responsible for catalytic activity and sterol-regulated degradation.Online Journal of Public Health Informatics, 1985
- Rapid and efficient site-specific mutagenesis without phenotypic selection.Proceedings of the National Academy of Sciences of the United States of America, 1985