title: Network of brain protein level changes in glutaminase deficient fetal mice.
abstract: Glutaminase is a multifunctional enzyme encoded by gene Gls involved in energy metabolism, ammonia trafficking and regeneration of neurotransmitter glutamate. To address the proteomic basis for the neurophenotypes of glutaminase-deficient mice, brain proteins from late gestation wild type, Gls+/- and Gls-/- male mice were subjected to two-dimensional gel electrophoresis, with subsequent identification by mass spectrometry using nano-LC-ESI-MS/MS. Protein spots that showed differential genotypic variation were quantified by immunoblotting. Differentially expressed proteins unambiguously identified by MS/MS included neurocalcin delta, retinol binding protein-1, reticulocalbin-3, cytoskeleton proteins fascin and tropomyosin alpha-4-chain, dihydropyrimidinase-related protein-5, apolipoprotein IV and proteins from protein metabolism proteasome subunits alpha type 2, type 7, heterogeneous nuclear ribonucleoprotein C1/C2 and H, voltage-gated anion-selective channel proteins 1 and 2, ATP synthase subunit β and transitional endoplasmic reticulum ATPase. An interaction network determined by Ingenuity Pathway Analysis revealed a link between glutaminase and calcium, Akt and retinol signaling, cytoskeletal elements, ATPases, ion channels, protein synthesis and the proteasome system, intermediary, nucleic acid and lipid metabolism, huntingtin, guidance cues, transforming growth factor beta-1 and hepatocyte nuclear factor 4-alpha. The network identified involves (a) cellular assembly and organization and (b) cell signaling and cell cycle, suggesting that Gls is crucial for neuronal maturation.
authors: Department of Pediatrics, Medical University of Vienna, Währinger Gürtel 18, 1090 Vienna, Austria.
authors: Narkhyun
authors: N
authors: Bae
authors: Yvonne
authors: Y
authors: Wang
authors: Lin
authors: L
authors: Li
authors: Stephen
authors: S
authors: Rayport
authors: Gert
authors: G
authors: Lubec
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology; D001923:Brain Chemistry; D015180:Electrophoresis, Gel, Two-Dimensional; D005333:Fetus / Q000378:metabolism; D005972:Glutaminase / Q000172:deficiency*; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D040901:Proteomics; D015398:Signal Transduction / Q000235:genetics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D009419:Nerve Tissue Proteins; D005972:Glutaminase
references: PLoS One. 2012;7(6):e38380
references: 22679499
references: Int J Biochem Cell Biol. 2009 Oct;41(10):2051-61
references: 19703661
references: Eur J Neurosci. 2008 Sep;28(6):1049-59
references: 18783370
references: Neuropsychopharmacology. 2008 May;33(6):1343-53
references: 17637606
references: J Biol Chem. 2012 Jun 22;287(26):21599-614
references: 22556411
references: J Neurosci. 2007 Aug 22;27(34):9192-200
references: 17715355
references: J Neurochem. 1995 Aug;65(2):871-81
references: 7616248
references: Biochem Soc Trans. 1987 Apr;15(2):208-10
references: 2884147
references: Expert Opin Ther Targets. 2005 Aug;9(4):639-50
references: 16083335
references: J Neurochem. 2012 Apr;121(2):184-96
references: 22309504
references: Dis Markers. 2008;24(4-5):251-5
references: 18525119
references: J Cereb Blood Flow Metab. 2012 May;32(5):816-24
references: 22373647
references: J Biol Chem. 2002 Oct 11;277(41):38939-44
references: 12163477
references: Neurochem Int. 2008 Mar-Apr;52(4-5):809-25
references: 18006192
references: Neuropsychopharmacology. 2009 Sep;34(10):2305-22
references: 19516252
references: Neurochem Int. 2009 Jul-Aug;55(1-3):64-70
references: 19428808
references: Nat Neurosci. 2011 Aug 14;14(9):1112-4
references: 21841774
references: Annu Rev Nutr. 1995;15:133-59
references: 8527215
references: Neurochem Res. 1983 Jan;8(1):25-38
references: 6856016
references: Psychopharmacology (Berl). 2008 May;198(1):1-27
references: 18392810
references: Mol Cell Proteomics. 2004 Jun;3(6):531-3
references: 15075378
references: Biochem J. 2006 May 15;396(1):51-9
references: 16433634
references: Arch Gen Psychiatry. 2009 Sep;66(9):938-46
references: 19736350
references: Electrophoresis. 2001 Jan;22(1):172-9
references: 11197169
references: Mol Cell Neurosci. 2011 Mar;46(3):633-44
references: 21236345
references: Trends Neurosci. 2004 Dec;27(12):735-43
references: 15541514
references: J Biol Chem. 1995 Jan 20;270(3):1185-90
references: 7836378
references: J Neurosci. 2006 Apr 26;26(17):4660-71
references: 16641247
references: Int J Geriatr Psychiatry. 2003 Sep;18(Suppl 1):S33-40
references: 12973748
references: Am J Psychiatry. 2002 Jul;159(7):1165-73
references: 12091195
references: Cell. 2010 Jul 9;142(1):144-57
references: 20603020
references: Mamm Genome. 2000 Dec;11(12):1107-10
references: 11130979
references: Cell. 2005 Jul 29;122(2):261-73
references: 16051150
references: Neuron. 2003 Jun 19;38(6):915-28
references: 12818177
references: J Neurochem. 1993 Nov;61(5):1795-800
references: 7901333
references: Eur J Neurosci. 2006 Jun;23(12):3375-84
references: 16820027
references: PLoS Genet. 2007 May 11;3(5):e82
references: 17500595
references: J Neurochem. 1990 Jun;54(6):2057-69
references: 1971010
references: PLoS One. 2009 Nov 19;4(11):e7901
references: 19936256
references: Physiol Genomics. 1999 Aug 31;1(2):51-62
references: 11015561
references: Neurochem Res. 2000 Oct;25(9-10):1407-19
references: 11059811
references: J Endocrinol. 2012 Mar;212(3):383-94
references: 22219301
references: Cereb Cortex. 2010 Mar;20(3):661-71
references: 19587023
references: Nat Neurosci. 2011 Jun 19;14(7):821-3
references: 21685919
references: Prog Neurobiol. 1979;13(3):277-323
references: 42117
references: J Biol Chem. 1990 Oct 15;265(29):17764-70
references: 2211660
references: J Neurosci. 2004 Jul 14;24(28):6352-61
references: 15254091
references: Development. 1999 Mar;126(6):1317-26
references: 10021349
references: Schizophr Res. 2005 Jun 1;75(1):27-34
references: 15820321
references: J Neurosci Res. 1991 Apr;28(4):531-48
references: 1714509
references: J Am Soc Nephrol. 2005 Oct;16(10):2852-63
references: 16079266
references: Neurochem Int. 2009 Jul-Aug;55(1-3):76-84
references: 19428810
references: BMC Cancer. 2004 Aug 25;4:56
references: 15329151
references: Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15653-8
references: 16230605
references: Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7455-60
references: 20378837
references: J Neurosci. 2004 Feb 4;24(5):1136-48
references: 14762132
references: Mol Psychiatry. 2005 Jan;10(1):40-68; image 5
references: 15263907
references: J Mol Biol. 2005 Feb 11;346(1):83-9
references: 15663929