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Cellular expression and localization of DGKζ-interacting NAP1-like proteins in the brain and functional implications under hypoxic stress

Histochemistry and Cell Biology Aims and scope Submit manuscript

Abstract

Diacylglycerol kinase (DGK) catalyzes conversion of a lipid second messenger diacylglycerol to another messenger molecule phosphatidic acid. Consequently, DGK plays a pivotal role in cellular pathophysiology by regulating the levels of these two messengers. We reported previously that DGKζ translocates from the nucleus to cytoplasm in hippocampal neurons under ischemic/hypoxic stress. In addition, we also identified nucleosome assembly protein 1 (NAP1)-like proteins NAP1L1 and NAP1L4 as novel DGKζ-interacting partners using a proteomic approach and revealed that these NAP1-like proteins induce cytoplasmic translocation of DGKζ in overexpressed cells because NAP1-like proteins associate with the nuclear localization signal of DGKζ and block its nuclear import via importin α. In the present study, we examined whether NAP1-like proteins are expressed in the brain and whether the molecular interaction of DGKζ and NAP1-like proteins would be changed in the brain after hypoxic stress. Immunohistochemistry revealed that NAP1L1 and NAP1L4 are widely expressed in neurons and glial cells in the brain with some differences. After 3 days of transient whole-body hypoxic stress, DGKζ translocated from the nucleus to cytoplasm in hippocampal pyramidal neurons, whereas NAP1-like proteins remained in the cytoplasm. Contrary to our expectations, NAP1-like proteins showed no change in their expression levels. The molecular interaction between DGKζ and NAP1-like proteins was attenuated after hypoxic stress. These results suggest that DGKζ cytoplasmic translocation in neurons under hypoxic stress is regulated by some mechanism which differs from that mediated by NAP1-like proteins.

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References

  • Abramovici H, Hogan AB, Obagi C, Topham MK, Gee SH (2003) Diacylglycerol kinase-ζ localization in skeletal muscle is regulated by phosphorylation and interaction with syntrophins. Mol Biol Cell 14:4499–4511

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Ali H, Nakano T, Saino-Saito S, Hozumi Y, Katagiri Y, Kamii H, Sato S, Kayama T, Kondo H, Goto K (2004) Selective translocation of diacylglycerol kinase ζ in hippocampal neurons under transient forebrain ischemia. Neurosci Lett 372:190–195

    Article  PubMed  CAS  Google Scholar 

  • Asahara H, Tartare-Deckert S, Nakagawa T, Ikehara T, Hirose F, Hunter T, Ito T, Montminy M (2002) Dual roles of p300 in chromatin assembly and transcriptional activation in cooperation with nucleosome assembly protein 1 in vitro. Mol Cell Biol 22:2974–2983

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Brindley DN, English D, Pilquil C, Buri K, Ling ZC (2002) Lipid phosphate phosphatases regulate signal transduction through glycerolipids and sphingolipids. Biochim Biophys Acta 1582:33–44

    Article  PubMed  CAS  Google Scholar 

  • Cockcroft S, Thomas GM (1992) Inositol-lipid-specific phospholipase C isoenzymes and their differential regulation by receptors. Biochem J 288:1–14

    PubMed  CAS  PubMed Central  Google Scholar 

  • Deng X, Wang Y, Chou J, Cadet JL (2001) Methamphetamine causes widespread apoptosis in the mouse brain: evidence from using an improved TUNEL histochemical method. Brain Res Mol Brain Res 93:64–69

    Article  PubMed  CAS  Google Scholar 

  • Evangelisti C, Bortul R, Fala F, Tabellini G, Goto K, Martelli AM (2007a) Nuclear diacylglycerol kinases: emerging downstream regulators in cell signaling networks. Histol Histopathol 22:573–579

    PubMed  CAS  Google Scholar 

  • Evangelisti C, Tazzari PL, Riccio M, Fiume R, Hozumi Y, Fala F, Goto K, Manzoli L, Cocco L, Martelli AM (2007b) Nuclear diacylglycerol kinase-ζ is a negative regulator of cell cycle progression in C2C12 mouse myoblasts. FASEB J 21:3297–3307

    Article  PubMed  CAS  Google Scholar 

  • Goto K, Hozumi Y, Kondo H (2006) Diacylglycerol, phosphatidic acid, and the converting enzyme, diacylglycerol kinase, in the nucleus. Biochim Biophys Acta 1761:535–541

    Article  PubMed  CAS  Google Scholar 

  • Goto K, Hozumi Y, Nakano T, Saino SS, Kondo H (2007) Cell biology and pathophysiology of the diacylglycerol kinase family: morphological aspects in tissues and organs. Int Rev Cytol 264:25–63

    Article  PubMed  CAS  Google Scholar 

  • Goto K, Tanaka T, Nakano T, Okada M, Hozumi Y, Topham MK, Martelli AM (2014) DGKζ under stress conditions: to be nuclear or cytoplasmic, that is the question. Adv Biol Regul 54:242–253

  • Hogan A, Shepherd L, Chabot J, Quenneville S, Prescott SM, Topham MK, Gee SH (2001) Interaction of γ1-syntrophin with diacylglycerol kinase-ζ. Regulation of nuclear localization by PDZ interactions. J Biol Chem 276:26526–26533

    Article  PubMed  CAS  Google Scholar 

  • Houser CR, Esclapez M (1996) Vulnerability and plasticity of the GABA system in the pilocarpine model of spontaneous recurrent seizures. Epilepsy Res 26:207–218

    Article  PubMed  CAS  Google Scholar 

  • Hozumi Y, Ito T, Nakano T, Nakagawa T, Aoyagi M, Kondo H, Goto K (2003) Nuclear localization of diacylglycerol kinase ζ in neurons. Eur J Neurosci 18:1448–1457

    Article  PubMed  Google Scholar 

  • Kanoh H, Yamada K, Sakane F (1990) Diacylglycerol kinase: a key modulator of signal transduction? Trends Biochem Sci 15:47–50

    Article  PubMed  CAS  Google Scholar 

  • Los AP, Vinke FP, de Widt J, Topham MK, van Blitterswijk WJ, Divecha N (2006) The retinoblastoma family proteins bind to and activate diacylglycerol kinase ζ. J Biol Chem 281:858–866

    Article  PubMed  CAS  Google Scholar 

  • Lowenstein DH, Thomas MJ, Smith DH, McIntosh TK (1992) Selective vulnerability of dentate hilar neurons following traumatic brain injury: a potential mechanistic link between head trauma and disorders of the hippocampus. J Neurosci 12:4846–4853

    PubMed  CAS  Google Scholar 

  • Luo B, Prescott SM, Topham MK (2003) Association of diacylglycerol kinase ζ with protein kinase C α: spatial regulation of diacylglycerol signaling. J Cell Biol 160:929–937

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Luo B, Prescott SM, Topham MK (2004) Diacylglycerol kinase ζ regulates phosphatidylinositol 4-phosphate 5-kinase Iα by a novel mechanism. Cell Signal 16:891–897

    Article  PubMed  CAS  Google Scholar 

  • Martelli AM, Ognibene A, Buontempo F, Fini M, Bressanin D, Goto K, McCubrey JA, Cocco L, Evangelisti C (2011) Nuclear phosphoinositides and their roles in cell biology and disease. Crit Rev Biochem Mol Biol 46:436–457

    Article  PubMed  CAS  Google Scholar 

  • Matsuyama T, Tsuchiyama M, Nakamura H, Matsumoto M, Sugita M (1993) Hilar somatostatin neurons are more vulnerable to an ischemic insult than CA1 pyramidal neurons. J Cereb Blood Flow Metab 13:229–234

    Article  PubMed  CAS  Google Scholar 

  • Merida I, Avila-Flores A, Merino E (2008) Diacylglycerol kinases: at the hub of cell signalling. Biochem J 409:1–18

    Article  PubMed  CAS  Google Scholar 

  • Mosammaparast N, Ewart CS, Pemberton LF (2002) A role for nucleosome assembly protein 1 in the nuclear transport of histones H2A and H2B. EMBO J 21:6527–6538

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Nakagawa S, Watanabe M, Isobe T, Kondo H, Inoue Y (1998) Cytological compartmentalization in the staggerer cerebellum, as revealed by calbindin immunohistochemistry for Purkinje cells. J Comp Neurol 395:112–120

    Article  PubMed  CAS  Google Scholar 

  • Nakamura M, Sato K, Fukaya M, Araishi K, Aiba A, Kano M, Watanabe M (2004) Signaling complex formation of phospholipase Cβ4 with metabotropic glutamate receptor type 1α and 1,4,5-trisphosphate receptor at the perisynapse and endoplasmic reticulum in the mouse brain. Eur J Neurosci 20:2929–2944

    Article  PubMed  Google Scholar 

  • Nakano T, Hozumi Y, Iwazaki K, Okumoto K, Iseki K, Saito T, Kawata S, Wakabayashi I, Goto K (2012) Altered expression of diacylglycerol kinase isozymes in regenerating liver. J Histochem Cytochem 60:130–138

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Nelson CD, Perry SJ, Regier DS, Prescott SM, Topham MK, Lefkowitz RJ (2007) Targeting of diacylglycerol degradation to M1 muscarinic receptors by β-arrestins. Science 315:663–666

    Article  PubMed  CAS  Google Scholar 

  • Nishizuka Y (1992) Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science 258:607–614

    Article  PubMed  CAS  Google Scholar 

  • Obenaus A, Esclapez M, Houser CR (1993) Loss of glutamate decarboxylase mRNA-containing neurons in the rat dentate gyrus following pilocarpine-induced seizures. J Neurosci 13:4470–4485

    PubMed  CAS  Google Scholar 

  • Okada M, Hozumi Y, Ichimura T, Tanaka T, Hasegawa H, Yamamoto M, Takahashi N, Iseki K, Yagisawa H, Shinkawa T, Isobe T, Goto K (2011) Interaction of nucleosome assembly proteins abolishes nuclear localization of DGKζ by attenuating its association with importins. Exp Cell Res 317:2853–2863

    Article  PubMed  CAS  Google Scholar 

  • Okada M, Hozumi Y, Tanaka T, Suzuki Y, Yanagida M, Araki Y, Evangelisti C, Yagisawa H, Topham MK, Martelli AM, Goto K (2012) DGKζ is degraded through the cytoplasmic ubiquitin-proteasome system under excitotoxic conditions, which causes neuronal apoptosis because of aberrant cell cycle reentry. Cell Signal 24:1573–1582

    Article  PubMed  CAS  Google Scholar 

  • Okuwaki M, Kato K, Nagata K (2010) Functional characterization of human nucleosome assembly protein 1-like proteins as histone chaperones. Genes Cells 15:13–27

    Article  PubMed  CAS  Google Scholar 

  • Palay S, Chan-Palay V (1974) Cerebellar cortex: cytology and organization. Springer, Berlin

    Book  Google Scholar 

  • Rehtanz M, Schmidt HM, Warthorst U, Steger G (2004) Direct interaction between nucleosome assembly protein 1 and the papillomavirus E2 proteins involved in activation of transcription. Mol Cell Biol 24:2153–2168

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Rhee SG, Suh PG, Ryu SH, Lee SY (1989) Studies of inositol phospholipid-specific phospholipase C. Science 244:546–550

    Article  PubMed  CAS  Google Scholar 

  • Rincon E, Gharbi SI, Santos-Mendoza T, Merida I (2012) Diacylglycerol kinase ζ: at the crossroads of lipid signaling and protein complex organization. Prog Lipid Res 51:1–10

    Article  PubMed  CAS  Google Scholar 

  • Saino-Saito S, Hozumi Y, Goto K (2011) Excitotoxicity by kainate-induced seizure causes diacylglycerol kinase ζ to shuttle from the nucleus to the cytoplasm in hippocampal neurons. Neurosci Lett 494:185–189

    Article  PubMed  CAS  Google Scholar 

  • Sakane F, Imai S, Kai M, Yasuda S, Kanoh H (2007) Diacylglycerol kinases: why so many of them? Biochim Biophys Acta 1771:793–806

    Article  PubMed  CAS  Google Scholar 

  • Sandager-Nielsen K, Andersen MB, Sager TN, Werge T, Scheel-Kruger J (2004) Effects of postnatal anoxia on striatal dopamine metabolism and prepulse inhibition in rats. Pharmacol Biochem Behav 77:767–774

    Article  PubMed  CAS  Google Scholar 

  • Sciorra VA, Morris AJ (2002) Roles for lipid phosphate phosphatases in regulation of cellular signaling. Biochim Biophys Acta 1582:45–51

    Article  PubMed  CAS  Google Scholar 

  • Sloviter RS (1987) Decreased hippocampal inhibition and a selective loss of interneurons in experimental epilepsy. Science 235:73–76

    Article  PubMed  CAS  Google Scholar 

  • Suzuki Y, Yamazaki Y, Hozumi Y, Okada M, Tanaka T, Iseki K, Ohta N, Aoyagi M, Fujii S, Goto K (2012) NMDA receptor-mediated Ca2+ influx triggers nucleocytoplasmic translocation of diacylglycerol kinase ζ under oxygen-glucose deprivation conditions, an in vitro model of ischemia, in rat hippocampal slices. Histochem Cell Biol 137:499–511

    Article  PubMed  CAS  Google Scholar 

  • Tanaka T, Okada M, Hozumi Y, Tachibana K, Kitanaka C, Hamamoto Y, Martelli AM, Topham MK, Iino M, Goto K (2013) Cytoplasmic localization of DGKζ exerts a protective effect against p53-mediated cytotoxicity. J Cell Sci 126:2785–2797

    Article  PubMed  CAS  Google Scholar 

  • Topham MK, Epand RM (2009) Mammalian diacylglycerol kinases: molecular interactions and biological functions of selected isoforms. Biochim Biophys Acta 1790:416–424

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Topham MK, Prescott SM (2001) Diacylglycerol kinase ζ regulates Ras activation by a novel mechanism. J Cell Biol 152:1135–1143

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Topham MK, Bunting M, Zimmerman GA, McIntyre TM, Blackshear PJ, Prescott SM (1998) Protein kinase C regulates the nuclear localization of diacylglycerol kinase-ζ. Nature 394:697–700

    Article  PubMed  CAS  Google Scholar 

  • Wakelam MJ (1998) Diacylglycerol—when is it an intracellular messenger? Biochim Biophys Acta 1436:117–126

    Article  PubMed  CAS  Google Scholar 

  • Yakubchyk Y, Abramovici H, Maillet JC, Daher E, Obagi C, Parks RJ, Topham MK, Gee SH (2005) Regulation of neurite outgrowth in N1E−115 cells through PDZ-mediated recruitment of diacylglycerol kinase ζ. Mol Cell Biol 25:7289–7302

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Zhang Y, Du G (2009) Phosphatidic acid signaling regulation of Ras superfamily of small guanosine triphosphatases. Biochim Biophys Acta 1791:850–855

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Zlatanova J, Seebart C, Tomschik M (2007) Nap1: taking a closer look at a juggler protein of extraordinary skills. FASEB J 21:1294–1310

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by grant-in-aid from The Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (K.G.).

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Correspondence to Kaoru Goto.

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Takahashi, N., Hozumi, Y., Tanaka, T. et al. Cellular expression and localization of DGKζ-interacting NAP1-like proteins in the brain and functional implications under hypoxic stress. Histochem Cell Biol 142, 461–471 (2014). https://doi.org/10.1007/s00418-014-1226-x

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  • DOI: https://doi.org/10.1007/s00418-014-1226-x

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