BMB Reports

생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
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Deciphering the molecular mechanisms underlying the plasma membrane targeting of PRMT8

  • Park, Sang-Won (Department of Ecological Science, College of Ecology and Environment, Kyungpook National University) ;
  • Jun, Yong-Woo (Department of Ecological Science, College of Ecology and Environment, Kyungpook National University) ;
  • Choi, Ha-Eun (Department of Biological Science and Biotechnology, College of Life Science and Nano Technology, Hannam University) ;
  • Lee, Jin-A (Department of Biological Science and Biotechnology, College of Life Science and Nano Technology, Hannam University) ;
  • Jang, Deok-Jin (Department of Ecological Science, College of Ecology and Environment, Kyungpook National University)
  • 투고 : 2018.11.29
  • 심사 : 2019.01.16
  • 발행 : 2019.10.31
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초록

Arginine methylation plays crucial roles in many cellular functions including signal transduction, RNA transcription, and regulation of gene expression. Protein arginine methyltransferase 8 (PRMT8), a unique brain-specific protein, is localized to the plasma membrane. However, the detailed molecular mechanisms underlying PRMT8 plasma membrane targeting remain unclear. Here, we demonstrate that the N-terminal 20 amino acids of PRMT8 are sufficient for plasma membrane localization and that oligomerization enhances membrane localization. The basic amino acids, combined with myristoylation within the N-terminal 20 amino acids of PRMT8, are critical for plasma membrane targeting. We also found that substituting Gly-2 with Ala [PRMT8(G2A)] or Cys-9 with Ser [PRMT8(C9S)] induces the formation of punctate structures in the cytosol or patch-like plasma membrane localization, respectively. Impairment of PRMT8 oligomerization/dimerization by C-terminal deletion induces PRMT8 mis-localization to the mitochondria, prevents the formation of punctate structures by PRMT8(G2A), and inhibits PRMT8(C9S) patch-like plasma membrane localization. Overall, these results suggest that oligomerization/dimerization plays several roles in inducing the efficient and specific plasma membrane localization of PRMT8.

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참고문헌

  1. Blanc RS and Richard S (2017) Arginine Methylation: The Coming of Age. Molecular cell 65, 8-24. https://doi.org/10.1016/j.molcel.2016.11.003
  2. Bedford MT and Clarke SG (2009) Protein arginine methylation in mammals: who, what, and why. Mol cell 33, 1-13 https://doi.org/10.1016/j.molcel.2008.12.013
  3. Morales Y, Caceres T, May K and Hevel JM (2016) Biochemistry and regulation of the protein arginine methyltransferases (PRMTs). Arch Biochem Biophys 590, 138-152 https://doi.org/10.1016/j.abb.2015.11.030
  4. Wolf SS (2009) The protein arginine methyltransferase family: an update about function, new perspectives and the physiological role in humans. Cell Mol Life Sci 66, 2109-2121 https://doi.org/10.1007/s00018-009-0010-x
  5. Feng Y, Maity R, Whitelegg JP et al (2013) Mammalian protein arginine methyltransferase 7 (PRMT7) specifically targets RXR sites in lysine- and arginine-rich regions. J Biol Chem 288, 37010-37025 https://doi.org/10.1074/jbc.M113.525345
  6. Kousaka A, Mori Y, Koyama Y, Taneda T, Miyata S and Tohyama M (2009) The distribution and characterization of endogenous protein arginine N-methyltransferase 8 in mouse CNS. Neuroscience 163, 1146-1157 https://doi.org/10.1016/j.neuroscience.2009.06.061
  7. Lee J, Sayegh J, Daniel J, Clarke S and Bedford M (2005) PRMT8, a new membrane-bound tissue-specific member of the protein arginine methyltransferase family. J Biol Chem 280, 32890-32896 https://doi.org/10.1074/jbc.M506944200
  8. Sayegh J, Webb K, Cheng D, Bedford MT and Clarke SG (2007) Regulation of protein arginine methyltransferase 8 (PRMT8) activity by its N-terminal domain. J Biol Chem 282, 36444-36453 https://doi.org/10.1074/jbc.M704650200
  9. Kim JD, Park K, Ishida J et al (2015) PRMT8 as a phospholipase regulates Purkinje cell dendritic arborization and motor coordination. Sci Adv 1, e1500615 https://doi.org/10.1126/sciadv.1500615
  10. Penney J, Seo J, Kritskiy O and Elmsaouri S (2017) Loss of Protein Arginine Methyltransferase 8 Alters Synapse Composition and Function, Resulting in Behavioral Defects. J Neurosci 37, 8655-8666 https://doi.org/10.1523/JNEUROSCI.0591-17.2017
  11. Lee PK, Goh WW and Sng JC (2017) Network-based characterization of the synaptic proteome reveals that removal of epigenetic regulator Prmt8 restricts proteins associated with synaptic maturation. J Neurochem 140, 613-62 https://doi.org/10.1111/jnc.13921
  12. Simandi Z, Paje, K, Karolyi K and Sieler T (2018) Arginine Methyltransferase PRMT8 Provides Cellular Stress Tolerance in Aging Motoneurons. J Neurosci 38, 7683-7700 https://doi.org/10.1523/JNEUROSCI.3389-17.2018
  13. Schapira M and Ferreira de Freitas R (2014) Structural biology and chemistry of protein arginine methyltransferases. Medchemcomm 5, 1779-178 https://doi.org/10.1039/C4MD00269E
  14. Toma-Fukai S, Kim JD, Park KE et al (2016) Novel helical assembly in arginine methyltransferase 8. J Mol Biol 428, 1197-1208 https://doi.org/10.1016/j.jmb.2016.02.007
  15. Jun YW, Lee SH, Shim J et al (2016) Dual roles of the N-terminal coiled-coil domain of an Aplysia sec7 protein: homodimer formation and nuclear export. J Neurochem 139, 1102-1112 https://doi.org/10.1111/jnc.13875
  16. Kim KH, Jun YW, Park Y et al (2014) Intracellular membrane association of the Aplysia cAMP phosphodiesterase long and short forms via different targeting mechanisms. J Biol Chem 289, 25797-25811 https://doi.org/10.1074/jbc.M114.572222
  17. McLaughlin S and Aderem A (1995) The myristoylelectrostatic switch: a modulator of reversible proteinmembrane interactions. Trends Biochem Sci 20, 272-276 https://doi.org/10.1016/S0968-0004(00)89042-8
  18. Swierczynski SL and Blackshear PJ (1996) Myristoylationdependent and electrostatic interactions exert independent effects on the membrane association of the myristoylated alanine-rich protein kinase C substrate protein in intact cells. J Biol Chem 271, 23424-23430. https://doi.org/10.1074/jbc.271.38.23424
  19. Jang DJ and Lee JA (2016) The roles of phosphoinositides in mammalian autophagy. Arch Pharm Res 39, 1129-36 https://doi.org/10.1007/s12272-016-0777-x
  20. Roise D and Schatz G (1988) Mitochondrial presequences. J Biol Chem 263, 4509-4511 https://doi.org/10.1016/S0021-9258(18)68809-X
  21. Pfanner N (2000) Protein sorting: recognizing mitochondrial presequences. Curr Biol 10, R412-415 https://doi.org/10.1016/S0960-9822(00)00507-8
  22. Lin YL, Tsai YJ, Liu YF et al (2013) The critical role of protein arginine methyltransferase prmt8 in zebrafish embryonic and neural development is non-redundant with its paralogue prmt1. PLoS One 8, e55221 https://doi.org/10.1371/journal.pone.0055221
  23. Jeong HC, Park SJ, Choi JJ et al (2017) PRMT8 Controls the Pluripotency and Mesodermal Fate of Human Embryonic Stem Cells By Enhancing the PI3K/AKT/SOX2 Axis. Stem Cells 35, 2037-2049 https://doi.org/10.1002/stem.2642
  24. Lee YK, Jun YW, Choi HE et al (2017) Development of LC3/GABARAP sensors containing a LIR and a hydrophobic domain to monitor autophagy. EMBO J 36, 1100-1116 https://doi.org/10.15252/embj.201696315
  25. Shin CH, Ryu S and Kim HH (2017) hnRNPK-regulated PTOV1-AS1 modulates heme oxygenase-1 expression via miR-1207-5p. BMB Rep 50, 220-225 https://doi.org/10.5483/BMBRep.2017.50.4.024
  26. Jang E, Lee HR, Lee GH et al (2017) Bach2 represses the AP-1-driven induction of interleukin-2 gene transcription in CD4 T cells. BMB Rep 50, 472-477 https://doi.org/10.5483/BMBRep.2017.50.9.124
  27. Hwang HS, Choi MH and Kim HA (2018) 29-kDa FN-f inhibited autophagy through modulating localization of HMGB1 in human articular chondrocytes. BMB Rep 51, 508-513 https://doi.org/10.5483/BMBRep.2018.51.10.058