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01-01-2017 | Neurology and Preclinical Neurological Studies - Original Article

Proteomic profile of embryonic stem cells with low survival motor neuron protein is consistent with developmental dysfunction

Authors: Graham C. Parker, Nicholas J. Carruthers, Theresa Gratsch, Joseph A. Caruso, Paul M. Stemmer

Published in: Journal of Neural Transmission | Issue 1/2017

Abstract

Spinal muscular atrophy is an autosomal recessive motor neuron disease caused by a genetic defect carried by as many as one in 75 people. Unlike most neurological disorders, we know exactly what the genetic basis is of the disorder, but in spite of this, have little understanding of why the low levels of one protein, survival motor neuron protein, results in the specific progressive die back of only one cell type in the body, the motor neuron. Given the fact that all cells in the body of a patient with spinal muscular atrophy share the same low abundance of the protein throughout development, an appropriate approach is to ask how lower levels of survival motor neuron protein affects the proteome of embryonic stem cells prior to development. Convergent biostatistical analyses of a discovery proteomic analysis of these cells provide results that are consistent with the pathomechanistic fate of the developed motor neuron.

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Acsadi G, Lee I, Li X, Parker GC, Huttemann M (2009) Mitochondrial dysfunction in a neural cell model of spinal muscular atrophy. J Neurosci Res 87:2748–2756CrossRefPubMed

Acsadi G, Li X, Murphy KJ, Swoboda KJ, Parker GC (2011) Alpha-synuclein loss in spinal muscular atrophy. J Mol Neurosci 43:275–283CrossRefPubMed

Bai CB, Stephen D, Joyner AL (2004) All mouse ventral spinal cord patterning by hedgehog is Gli dependent and involves an activator function of Gli3. Dev Cell 6:103–115CrossRefPubMed

Bendall SC, Hughes C, Stewart MH et al (2008) Prevention of amino acid conversion in SILAC experiments with embryonic stem cells. Mol Cell Proteom 7:1587–1597CrossRef

Bowerman M, Anderson CL, Beauvais A et al (2009) SMN, profilin IIa and plastin 3: a link between the deregulation of actin dynamics and SMA pathogenesis. Mol Cell Neurosci 42:66–74CrossRefPubMed

Brzustowicz LM, Lehner T, Castilla LH et al (1990) Genetic mapping of chronic childhood-onset spinal muscular atrophy to chromosome 5q11.2-13.3. Nature 344:540–541CrossRefPubMed

Burd L, Short SK, Martsolf JT et al (1991) Prevalence of type I spinal muscular atrophy in North Dakota. Am J Med Genet 41:212–215CrossRefPubMed

Burghes AH, Beattie CE (2009) Spinal muscular atrophy: why do low levels of survival motor neuron protein make motor neurons sick? Nat Rev Neurosci 10:597–609CrossRefPubMedPubMedCentral

Carruthers NJ, Parker GC, Gratsch T et al (2015) Protein mobility shifts contribute to gel electrophoresis liquid chromatography analysis. J Biomol Tech 26:103–112CrossRefPubMedPubMedCentral

Conforti L, Gilley J, Coleman MP (2014) Wallerian degeneration: an emerging axon death pathway linking injury and disease. Nat Rev Neurosci 15:394–409CrossRefPubMed

Dillon AK, Fujita SC, Matise MP et al (2005) Molecular control of spinal accessory motor neuron/axon development in the mouse spinal cord. J Neurosci 25:10119–10130CrossRefPubMed

Duncan JE, Little NK, Zungia A et al (2013) The microtubule regulatory protein Stathmin is required to maintain the integrity of axonal microtubules in Drosophila. PLoS One 8:e68324CrossRefPubMedPubMedCentral

Fischer U, Liu Q, Dreyfuss G (1997) The SMN-SIP1 complex has an essential role in spliceosomal snRNP biogenesis. Cell 90:1023–1029CrossRefPubMed

Gubitz AK, Feng W, Dreyfuss G (2004) The SMN complex. Exp Cell Res 296:51–56CrossRefPubMed

Hentze MW, Muckenthaler MU, Galy B et al (2010) Two to tango: regulation of Mammalian iron metabolism. Cell 142:24–38CrossRefPubMed

Huang da W, Sherman BT, Zheng X et al (2009) Extracting biological meaning from large gene lists with DAVID. Curr Protoc Bioinform. 27:13.11:13.11.1–13.11.13

Huang S, Laoukili J, Epping MT et al (2009) ZNF423 is critically required for retinoic acid-induced differentiation and is a marker of neuroblastoma outcome. Cancer Cell 15:328–340CrossRefPubMedPubMedCentral

Jeong SY, Crooks DR, Wilson-Ollivierre H et al (2011) Iron insufficiency compromises motor neurons and their mitochondrial function in Irp2-null mice. PLoS One 6:e25404CrossRefPubMedPubMedCentral

Krämer A, Green J, Pollard J Jr, Tugendreich S (2014) Causal analysis approaches in ingenuity pathway analysis. Bioinformatics 30:523–530CrossRefPubMed

Lefebvre S, Burglen L, Reboullet S et al (1995) Identification and characterization of a spinal muscular atrophy-determining gene. Cell 80:155–165CrossRefPubMed

Li M, Aliotta JM, Asara JM et al (2012) Quantitative proteomic analysis of exosomes from HIV-1 infected lymphocytic cells. Proteomics 12:2203–2211CrossRefPubMed

Lorson CL, Hahnen E, Androphy EJ, Wirth B (1999) A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. Proc Natl Acad Sci USA 96:6307–6311CrossRefPubMedPubMedCentral

Mazeyrat S, Saut N, Grigoriev V et al (2001) A Y-encoded subunit of the translation initiation factor Eif2 is essential for mouse spermatogenesis. Nat Genet 29:49–53CrossRefPubMed

Meister G, Hannus S, Plottner O et al (2001) SMNrp is an essential pre-mRNA splicing factor required for the formation of the mature spliceosome. EMBO J 20:2304–2314CrossRefPubMedPubMedCentral

Monani UR, Lorson CL, Parsons DW et al (1999) A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2. Hum Mol Genet 8:1177–1183CrossRefPubMed

Murayama S, Bouldin TW, Suzuki K (1991) Immunocytochemical and ultrastructural studies of Werdnig–Hoffmann disease. Acta Neuropathol (Berl) 81:408–417CrossRef

Ogino S, Wilson RB (2004) Spinal muscular atrophy: molecular genetics and diagnostics. Expert Rev Mol Diagn 4:15–29CrossRefPubMed

Pan ST, Zhou ZW, He ZX et al (2015) Proteomic response to 5,6-dimethylxanthenone 4-acetic acid (DMXAA, vadimezan) in human non-small cell lung cancer A549 cells determined by the stable-isotope labeling by amino acids in cell culture (SILAC) approach. Drug Des Devel Ther 9:937–968PubMedPubMedCentral

Parker GC, Li X, Anguelov RA et al (2008) Survival motor neuron protein regulates apoptosis in an in vitro model of spinal muscular atrophy. Neurotox Res 13:39–48CrossRefPubMed

Reimer MM, Kuscha V, Wyatt C et al (2009) Sonic hedgehog is a polarized signal for motor neuron regeneration in adult zebrafish. J Neurosci 29:15073–15082CrossRefPubMedPubMedCentral

Shin JE, Geisler S, DiAntonia A (2014) Dynamic regulation of SCG10 in regenerating axons after injury. Exp Neurol 252:1–11CrossRefPubMed

Subramanian A, Tamayo P, Mootha VK et al (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 102:15545–15550CrossRefPubMedPubMedCentral

Virgili M, Crochemore C, Peña-Altamira E et al (2006) Regional and temporal alterations of ODC/polyamine system during ALS-like neurodegenerative motor syndrome in G93A transgenic mice. Neurochem Int 48:201–207CrossRefPubMed

Vitte JM, Davoult B, Roblot N et al (2004) Deletion of murine Smn exon 7 directed to liver leads to severe defect of liver development associated with iron overload. Am J Pathol 165:1731–1741CrossRefPubMedPubMedCentral

Wirth B (2000) An update of the mutation spectrum of the survival motor neuron gene (SMN1) in autosomal recessive spinal muscular atrophy (SMA). Hum Mutat 15:228–237CrossRefPubMed

Yu J, Guo Y, Sun M et al (2009) Iron is a potential key mediator of glutamate excitotoxicity in spinal cord motor neurons. Brain Res 27:102–107CrossRef

Zhang Z, Lotti F, Dittmar K, Younis I et al (2008) SMN deficiency causes tissue-specific perturbations in the repertoire of snRNAs and widespread defects in splicing. Cell 133:585–600CrossRefPubMedPubMedCentral

Zumbrennen-Bullough KB, Becker L, Garrett L et al (2014) Abnormal brain iron metabolism in Irp2 deficient mice is associated with mild neurological and behavioral impairments. PLoS One 9:e98072CrossRefPubMedPubMedCentral

Title: Proteomic profile of embryonic stem cells with low survival motor neuron protein is consistent with developmental dysfunction
Authors: Graham C. Parker
Nicholas J. Carruthers
Theresa Gratsch
Joseph A. Caruso
Paul M. Stemmer
Publication date: 01-01-2017
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 1/2017
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-016-1520-y

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Proteomic profile of embryonic stem cells with low survival motor neuron protein is consistent with developmental dysfunction

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