Deciphering the molecular mechanisms underlying the plasma membrane targeting of PRMT8
2
조회
0
다운로드
2
인용
0
참고문헌
키워드
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 Cterminal 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.
Abstract
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 Cterminal 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.
참고문헌 (27)
- Blanc RS, "Arginine Methylation : The Coming of Age", Molecular cell, 65, pp.8~24 (2017)
- Bedford MT, "Protein arginine methylation in mammals : who, what, and why", Mol cell, 33, pp.1~13 (2009)
- Morales Y, "Biochemistry and regulation of the protein arginine methyltransferases(PRMTs)", Arch Biochem Biophys, 590, pp.138~152 (2016)
- Wolf SS, "The protein arginine methyltransferase family : an update about function, new perspectives and the physiological role in humans", Cell Mol Life Sci, 66, pp.2109~2121 (2009)
- Feng Y, "Mammalian protein arginine methyltransferase 7(PRMT7)specifically targets RXR sites in lysine-and arginine-rich regions", J Biol Chem, 288, pp.37010~37025 (2013)
- Kousaka A, "The distribution and characterization of endogenous protein arginine N-methyltransferase 8 in mouse CNS", Neuroscience, 163, pp.1146~1157 (2009)
- Lee J, "PRMT8, a new membrane-bound tissue-specific member of the protein arginine methyltransferase family", J Biol Chem, 280, pp.32890~32896 (2005)
- Sayegh J, "Regulation of protein arginine methyltransferase 8(PRMT8)activity by its N-terminal domain", J Biol Chem, 282, pp.36444~36453 (2007)
- Kim JD, "PRMT8 as a phospholipase regulates Purkinje cell dendritic arborization and motor coordination", Sci Adv, 1, pp.e1500615~ (2015)
- Penney J, "Loss of Protein Arginine Methyltransferase 8 Alters Synapse Composition and Function, Resulting in Behavioral Defects", J Neurosci, 37, pp.8655~8666 (2017)
- Lee PK, "Network-based characterization of the synaptic proteome reveals that removal of epigenetic regulator Prmt8 restricts proteins associated with synaptic maturation", J Neurochem, 140, pp.613~662 (2017)
- Simandi Z, "Arginine Methyltransferase PRMT8 Provides Cellular Stress Tolerance in Aging Motoneurons", J Neurosci, 38, pp.7683~7700 (2018)
- Schapira M, "Structural biology and chemistry of protein arginine methyltransferases", Medchemcomm, 5, pp.1779~1178 (2014)
- Toma-Fukai S, "Novel helical assembly in arginine methyltransferase 8", J Mol Biol, 428, pp.1197~1208 (2016)
- Jun YW, "Dual roles of the N-terminal coiled-coil domain of an Aplysia sec7 protein : homodimer formation and nuclear export", J Neurochem, 139, pp.1102~1112 (2016)
- Kim KH, "Intracellular membrane association of the Aplysia cAMP phosphodiesterase long and short forms via different targeting mechanisms", J Biol Chem, 289, pp.25797~25811 (2014)
- McLaughlin S, "The myristoylelectrostatic switch : a modulator of reversible proteinmembrane interactions", Trends Biochem Sci, 20, pp.272~276 (1995)
- Swierczynski SL, "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, pp.23424~23430 (1996)
- 장덕진, "The roles of phosphoinositides in mammalian autophagy", Archives of Pharmacal Research, 39(8), pp.1129~1136 (2016), 대한약학회
- Roise D, "Mitochondrial presequences", J Biol Chem, 263, pp.4509~4511 (1988)
- Pfanner N, "Protein sorting : recognizing mitochondrial presequences", Curr Biol, 10, pp.R412~W415 (2000)
- Lin YL, "The critical role of protein arginine methyltransferase prmt8 in zebrafish embryonic and neural development is non-redundant with its paralogue prmt1", PLoS One, 8, pp.e55221~ (2013)
- Jeong HC, "PRMT8 Controls the Pluripotency and Mesodermal Fate of Human Embryonic Stem Cells By Enhancing the PI3K", AKT, Stem Cells, pp.2017, 35[DOI]
- Lee YK, "Development of LC3", GABARAP sensors containing a LIR and a hydrophobic domain to monitor autophagy, 2017, pp.36, 1100~1116
- 신창훈, "hnRNPK-regulated PTOV1-AS1 modulates heme oxygenase-1 expression via miR-1207-5p", BMB Reports, 50(4), pp.220~225 (2017), 생화학분자생물학회
- 장은경, "Bach2 represses the AP-1-driven induction of interleukin-2 gene transcription in CD4＋ T cells", BMB Reports, 50(9), pp.472~477 (2017), 생화학분자생물학회
- 황현숙, "29-kDa FN-f inhibited autophagy through modulating localization of HMGB1 in human articular chondrocytes", BMB Reports, 51(10), pp.508~513 (2018), 생화학분자생물학회