A role for N-myristoylation in protein targeting: NADH-cytochrome b5 reductase requires myristic acid for association with outer mitochondrial but not ER membranes.

The Journal of Cell Biology
Nica BorgeseM Bassetti

Abstract

N-myristoylation is a cotranslational modification involved in protein-protein interactions as well as in anchoring polypeptides to phospholipid bilayers; however, its role in targeting proteins to specific subcellular compartments has not been clearly defined. The mammalian myristoylated flavoenzyme NADH-cytochrome b5 reductase is integrated into ER and mitochondrial outer membranes via an anchor containing a stretch of 14 uncharged amino acids downstream to the NH2-terminal myristoylate glycine. Since previous studies suggested that the anchoring function could be adequately carried out by the 14 uncharged residues, we investigated a possible role for myristic acid in reductase targeting. The wild type (wt) and a nonmyristoylatable reductase mutant (gly2-->ala) were stably expressed in MDCK cells, and their localization was investigated by immunofluorescence, immuno-EM, and cell fractionation. By all three techniques, the wt protein localized to ER and mitochondria, while the nonmyristoylated mutant was found only on ER membranes. Pulse-chase experiments indicated that this altered steady state distribution was due to the mutant's inability to target to mitochondria, and not to its enhanced instability in that location. Both ...Continue Reading

References

Dec 1, 1992·The Journal of Cell Biology·H M McBrideG C Shore
Dec 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·S Zozulya, L Stryer
Jan 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·T L JonesA M Spiegel
Jan 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·S M MumbyA G Gilman
Oct 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·G PietriniN Borgese
Apr 1, 1973·Virology·F L Graham, A J van der Eb
Jul 1, 1974·European Journal of Biochemistry·W M Bonner, R A Laskey
Oct 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·S A CarrK Titani
Jan 1, 1982·The Journal of Cell Biology·D LouvardG Warren
Dec 6, 1994·Proceedings of the National Academy of Sciences of the United States of America·C T SigalM D Resh
Nov 1, 1995·Experimental Cell Research·C D'Souza-Schorey, P D Stahl
Jul 1, 1995·Trends in Biochemical Sciences·S McLaughlin, A Aderem
Apr 14, 1995·Science·P J Casey
Jun 16, 1995·The Journal of Biological Chemistry·P A RandazzoR A Kahn
Jan 15, 1995·European Journal of Biochemistry·G C ShoreM Nguyen
Mar 3, 1995·The Journal of Biological Chemistry·J B AmesL Stryer
Jan 1, 1994·Annual Review of Cell Biology·P Walter, A E Johnson
Jan 1, 1994·Annual Review of Biochemistry·D R JohnsonJ I Gordon
Aug 12, 1994·Journal of Molecular Biology·M P Harris, J C Neil
Sep 1, 1993·The Journal of Membrane Biology·M KieblerW Neupert

❮ Previous
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Citations

Mar 21, 2000·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·K Mihara
Feb 2, 2006·Molecular Genetics and Genomics : MGG·Wentian LuoNeil Green
Mar 10, 2007·Apoptosis : an International Journal on Programmed Cell Death·Miroslav VarechaMichal Kozubek
Feb 9, 2002·The Journal of Nutritional Biochemistry·Vincent RiouxPhilippe Legrand
Mar 31, 2000·Bioorganic & Medicinal Chemistry Letters·J PengG D Prestwich
Dec 21, 2000·The Plant Journal : for Cell and Molecular Biology·P BagnaresiJ F Briat
May 8, 2004·The Journal of Biological Chemistry·Hao ZhuH Franklin Bunn
May 30, 2012·The Journal of General Physiology·Karin NowikovskyPaolo Bernardi
Jul 8, 2009·Journal of Biomedical Science·Miroslav VarechaMichal Kozubek
May 15, 2010·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Nobuhiro Hayashi, Koiti Titani
Oct 6, 2010·Biochimica Et Biophysica Acta·Vincent RiouxPhilippe Legrand
Aug 15, 2006·The European Journal of Neuroscience·Andrea RaimondiGrazia Pietrini
Jul 19, 2006·Progress in Lipid Research·Ponniah SelvakumarRajendra K Sharma
Mar 8, 2016·Traffic·Lars EllgaardIneke Braakman
Dec 20, 2007·Current Opinion in Clinical Nutrition and Metabolic Care·Vincent Rioux, Philippe Legrand
Jan 9, 1999·The Journal of Biological Chemistry·S N SarkarG C Sen
Jan 22, 2009·Médecine sciences : M/S·Erwan BeauchampPhilippe Legrand
Mar 16, 2006·Molecular and Cellular Biochemistry·Vincent RiouxPhilippe Legrand
Feb 1, 2017·Journal of Cell Science·Anthi DemetriadouPetros P Petrou

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