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Expression of Gas1 in Mouse Brain: Release and Role in Neuronal Differentiation

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Abstract

Growth arrest-specific 1 (Gas1) is a pleiotropic protein that induces apoptosis of tumor cells and has important roles during development. Recently, the presence of two forms of Gas1 was reported: one attached to the cell membrane by a GPI anchor; and a soluble extracellular form shed by cells. Previously, we showed that Gas1 is expressed in different areas of the adult mouse CNS. Here, we report the levels of Gas1 mRNA protein in different regions and analyzed its expressions in glutamatergic, GABAergic, and dopaminergic neurons. We found that Gas1 is expressed in GABAergic and glutamatergic neurons in the Purkinje-molecular layer of the cerebellum, hippocampus, thalamus, and fastigial nucleus, as well as in dopaminergic neurons of the substantia nigra. In all cases, Gas1 was found in the cell bodies, but not in the neuropil. The Purkinje and the molecular layers show the highest levels of Gas1, whereas the granule cell layer has low levels. Moreover, we detected the expression and release of Gas1 from primary cultures of Purkinje cells and from hippocampal neurons as well as from neuronal cell lines, but not from cerebellar granular cells. In addition, using SH-SY5Y cells differentiated with retinoic acid as a neuronal model, we found that extracellular Gas1 promotes neurite outgrowth, increases the levels of tyrosine hydroxylase, and stimulates the inhibition of GSK3β. These findings demonstrate that Gas1 is expressed and released by neurons and promotes differentiation, suggesting an important role for Gas1 in cellular signaling in the CNS.

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References

  • Agholme L, Lindstrom T, Kagedal K, Marcusson J, Hallbeck M (2010) An in vitro model for neuroscience: differentiation of SH-SY5Y cells into cells with morphological and biochemical characteristics of mature neurons. J Alzheimers Dis 20:1069–1082. doi:10.3233/JAD-2010-091363

    Article  CAS  PubMed  Google Scholar 

  • Ahlemeyer B, Baumgart-Vogt E (2005) Optimized protocols for the simultaneous preparation of primary neuronal cultures of the neocortex, hippocampus and cerebellum from individual newborn (P0.5) C57Bl/6 J mice. J Neurosci Methods 149:110–120. doi:10.1016/j.jneumeth.2005.05.022

    Article  CAS  PubMed  Google Scholar 

  • Allen BL, Tenzen T, McMahon AP (2007) The Hedgehog-binding proteins Gas1 and Cdo cooperate to positively regulate Shh signaling during mouse development. Genes Dev 21:1244–1257. doi:10.1101/gad.1543607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ayala-Sarmiento AE, Estudillo E, Perez-Sanchez G, Sierra-Sanchez A, Gonzalez-Mariscal L, Martinez-Fong D, Segovia J (2016) GAS1 is present in the cerebrospinal fluid and is expressed in the choroid plexus of the adult rat. Histochem Cell Biol 146:325–336. doi:10.1007/s00418-016-1449-0

    Article  CAS  PubMed  Google Scholar 

  • Bellocchio EE, Hu H, Pohorille A, Chan J, Pickel VM, Edwards RH (1998) The localization of the brain-specific inorganic phosphate transporter suggests a specific presynaptic role in glutamatergic transmission. J Neurosci 18:8648–8659

    Article  CAS  PubMed  Google Scholar 

  • Biau S, Jin S, Fan CM (2012) Gastrointestinal defects of the Gas1 mutant involve dysregulated Hedgehog and Ret signaling. Biol Open 2:144–155. doi:10.1242/bio.20123186

    Article  PubMed  PubMed Central  Google Scholar 

  • Cabrera JR, Sanchez-Pulido L, Rojas AM, Valencia A, Manes S, Naranjo JR, Mellstrom B (2006) Gas1 is related to the glial cell-derived neurotrophic factor family receptors alpha and regulates Ret signaling. J Biol Chem 281:14330–14339. doi:10.1074/jbc.M509572200

    Article  CAS  PubMed  Google Scholar 

  • Castelo-Branco G, Rawal N, Arenas E (2004) GSK-3beta inhibition/beta-catenin stabilization in ventral midbrain precursors increases differentiation into dopamine neurons. J Cell Sci 117:5731–5737. doi:10.1242/jcs.01505

    Article  CAS  PubMed  Google Scholar 

  • Chan MC, Bautista E, Alvarado-Cruz I, Quintanilla-Vega B, Segovia J (2017) Inorganic mercury prevents the differentiation of SH-SY5Y cells: amyloid precursor protein, microtubule associated proteins and ROS as potential targets. J Trace Elem Med Biol 41:119–128. doi:10.1016/j.jtemb.2017.02.002

    Article  CAS  PubMed  Google Scholar 

  • Chapuis J, Vingtdeux V, Campagne F, Davies P, Marambaud P (2011) Growth arrest-specific 1 binds to and controls the maturation and processing of the amyloid-precursor protein. Hum Mol Genet 20:2026–2036. doi:10.1093/hmg/ddr085

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chapuis J, Vingtdeux V, Capiralla H, Davies P, Marambaud P (2012) Gas1 interferes with AbetaPP trafficking by facilitating the accumulation of immature AbetaPP in endoplasmic reticulum-associated raft subdomains. J Alzheimers Dis 28:127–135. doi:10.3233/JAD-2011-110434

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen G, Bower KA, Ma C, Fang S, Thiele CJ, Luo J (2004) Glycogen synthase kinase 3beta (GSK3beta) mediates 6-hydroxydopamine-induced neuronal death. FASEB J 18:1162–1164. doi:10.1096/fj.04-1551fje

    Article  CAS  PubMed  Google Scholar 

  • Chen G, Bower KA, Xu M, Ding M, Shi X, Ke ZJ, Luo J (2009) Cyanidin-3-glucoside reverses ethanol-induced inhibition of neurite outgrowth: role of glycogen synthase kinase 3 Beta. Neurotox Res 15:321–331. doi:10.1007/s12640-009-9036-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheung YT, Lau WK, Yu MS, Lai CS, Yeung SC, So KF, Chang RC (2009) Effects of all-trans-retinoic acid on human SH-SY5Y neuroblastoma as in vitro model in neurotoxicity research. Neurotoxicology 30:127–135. doi:10.1016/j.neuro.2008.11.001

    Article  CAS  PubMed  Google Scholar 

  • Chou DK, Jungalwala FB (1996) N-Acetylglucosaminyl transferase regulates the expression of the sulfoglucuronyl glycolipids in specific cell types in cerebellum during development. J Biol Chem 271:28868–28874

    Article  CAS  PubMed  Google Scholar 

  • Cohen P, Frame S (2001) The renaissance of GSK3. Nat Rev Mol Cell Biol 2:769–776. doi:10.1038/35096075

    Article  CAS  PubMed  Google Scholar 

  • Constantinescu R, Constantinescu AT, Reichmann H, Janetzky B (2007) Neuronal differentiation and long-term culture of the human neuroblastoma line SH-SY5Y. In: Gerlach M, Deckert J, Double K, Koutsilieri E (eds) Neuropsychiatric Disorders An Integrative Approach. Springer Vienna, Australia, pp 17–28

    Chapter  Google Scholar 

  • Cuende J, Moreno S, Bolanos JP, Almeida A (2008) Retinoic acid downregulates Rae1 leading to APC(Cdh1) activation and neuroblastoma SH-SY5Y differentiation. Oncogene 27:3339–3344. doi:10.1038/sj.onc.1210987

    Article  CAS  PubMed  Google Scholar 

  • De Luca A, Cerrato V, Fucà E, Parmigiani E, Buffo A, Leto K (2016). Sonic hedgehog patterning during cerebellar development. Cell Mol Life Sci 73:291–303. doi:10.1007/s00018-015-2065-1

    Article  CAS  PubMed  Google Scholar 

  • Del Sal G, Ruaro ME, Philipson L, Schneider C (1992) The growth arrest-specific gene, gas1, is involved in growth suppression. Cell 70:595–607. doi:10.1016/0092-8674(92)90429-G

    Article  CAS  PubMed  Google Scholar 

  • Del Sal G, Collavin L, Ruaro ME, Edomi P, Saccone S, Valle GD, Schneider C (1994) Structure, function, and chromosome mapping of the growth-suppressing human homologue of the murine gas1 gene. Proc Natl Acad Sci U S A 91:1848–1852. doi:10.1073/pnas.91.5.1848

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Derfuss T, Parikh K, Velhin S, Braun M, Mathey E, Krumbholz M, Kümpfel T, Moldenhauer A, Rader C, Sonderegger P, Pöllmann W, Tiefenthaller C, Bauer J, Lassmann H, Wekerle H, Karagogeos D, Hohlfeld R, Linington C, Meinl E (2009) Contactin-2/TAG-1-directed autoimmunity is identified in multiple sclerosis patients and mediates gray matter pathology in animals. Proc Natl Acad Sci USA 106:8302–8307. doi:10.1073/pnas.0901496106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Encinas M, Iglesias M, Liu Y, Wang H, Muhaisen A, Ceña V, Gallego C, Comella JX (2000) Sequential treatment of SH-SY5Y cells with retinoic acid and brain-derived neurotrophic factor gives rise to fully differentiated, neurotrophic factor-dependent, human neuron-like cells. J Neurochem 75:991–1003

    Article  CAS  PubMed  Google Scholar 

  • Esclapez M, Tillakaratne NJ, Kaufman DL, Tobin AJ, Houser CR (1994) Comparative localization of two forms of glutamic acid decarboxylase and their mRNAs in rat brain supports the concept of functional differences between the forms. J Neurosci 14:1834–1855

    CAS  PubMed  Google Scholar 

  • Estudillo E, Zavala P, Perez-Sanchez G, Ayala-Sarmiento AE, Segovia J (2016) Gas1 is present in germinal niches of developing dentate gyrus and cortex. Cell Tissue Res 364:369–384. doi:10.1007/s00441-015-2338-x

    Article  CAS  PubMed  Google Scholar 

  • Feldblum S, Erlander MG, Tobin AJ (1993) Different distributions of GAD65 and GAD67 mRNAs suggest that the two glutamate decarboxylases play distinctive functional roles. J Neurosci Res 34:689–706. doi:10.1002/jnr.490340612

    Article  CAS  PubMed  Google Scholar 

  • Ferraro GB, Morrison CJ, Overall CM, Strittmatter SM, Fournier AE (2011) Membrane-type matrix metalloproteinase-3 regulates neuronal responsiveness to myelin through Nogo-66 receptor 1 cleavage. J Biol Chem 286:31418–31424. doi:10.1074/jbc.M111.249169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fremeau RT Jr, Troyer MD, Pahner I, Nygaard GO, Tran CH, Reimer RJ, Bellocchio EE, Fortin D, Storm-Mathisen J, Edwards RH (2001) The expression of vesicular glutamate transporters defines two classes of excitatory synapse. Neuron 31:247–260. doi:10.1016/S0896-6273(01)00344-0

    Article  CAS  PubMed  Google Scholar 

  • Fremeau RT Jr, Burman J, Qureshi T, Tran CH, Proctor J, Johnson J, Zhang H, Sulzer D, Copenhagen DR, Storm-Mathisen J, Reimer RJ, Chaudhry FA, Edwards RH (2002) The identification of vesicular glutamate transporter 3 suggests novel modes of signaling by glutamate. Proc Natl Acad Sci USA 99:14488–14493. doi:10.1073/pnas.222546799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fujiyama F, Hioki H, Tomioka R, Taki K, Tamamaki N, Nomura S, Okamoto K, Kaneko T (2003) Changes of immunocytochemical localization of vesicular glutamate transporters in the rat visual system after the retinofugal denervation. J Comp Neurol 465:234–249. doi:10.1002/cne.10848

    Article  CAS  PubMed  Google Scholar 

  • Fukusumi Y, Meier F, Götz S, Matheus F, Irmler M, Beckervordersandforth R, Faus-Kessler T, Minina E, Rauser B, Zhang J, Arenas E, Andersson E, Niehrs C, Beckers J, Simeone A, Wurst W, Prakash N (2015) Dickkopf 3 promotes the differentiation of a rostrolateral midbrain dopaminergic neuronal subset in vivo and from pluripotent stem cells in vitro in the mouse. J Neurosci 35:13385–13401. doi:10.1523/JNEUROSCI.1722-15.2015

    Article  CAS  PubMed  Google Scholar 

  • Furuya S, Makino A, Hirabayashi Y (1998) An improved method for culturing cerebellar Purkinje cells with differentiated dendrites under a mixed monolayer setting. Brain Res Brain Res Protoc 3:192–198. doi:10.1016/S1385-299X(98)00040-3

    Article  CAS  PubMed  Google Scholar 

  • Galderisi U, Jori FP, Giordano A (2003) Cell cycle regulation and neural differentiation. Oncogene 22:5208–5219. doi:10.1038/sj.onc.1206558

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Tovar CG, Perez A, Luna J, Mena R, Osorio B, Aleman V, Mondragon R, Mornet D, Rendón A, Hernandez JM (2001) Biochemical and histochemical analysis of 71 kDa dystrophin isoform (Dp71f) in rat brain. Acta Histochem 103:209–224. doi:10.1078/0065-1281-00591

    Article  CAS  PubMed  Google Scholar 

  • Garrido JJ, Simon D, Varea O, Wandosell F (2007) GSK3 alpha and GSK3 beta are necessary for axon formation. FEBS Lett 581:1579–1586. doi:10.1016/j.febslet.2007.03.018

    Article  CAS  PubMed  Google Scholar 

  • Gautam V, D’Avanzo C, Hebisch M, Kovacs DM, Kim DY (2014) BACE1 activity regulates cell surface contactin-2 levels. Mol Neurodegener 9:4. doi:10.1186/1750-1326-9-4

    Article  PubMed  PubMed Central  Google Scholar 

  • Gennarini G, Bizzoca A, Picocci S, Puzzo D, Corsi P, Furley AJW (2016) The role of Gpi-anchored axonal glycoproteins in neural development and neurological disorders. Mol Cell Neurosci 81:49–63. doi:10.1016/j.mcn.2016.11.006

    Article  PubMed  Google Scholar 

  • Gras C, Herzog E, Bellenchi GC, Bernard V, Ravassard P, Pohl M, Gasnier B, Giros B, El Mestikawy S (2002) A third vesicular glutamate transporter expressed by cholinergic and serotoninergic neurons. J Neurosci 22:5442–5451

    CAS  PubMed  Google Scholar 

  • Hernandez-Baltazar D, Mendoza-Garrido ME, Martinez-Fong D (2013) Activation of GSK-3beta and caspase-3 occurs in Nigral dopamine neurons during the development of apoptosis activated by a striatal injection of 6-hydroxydopamine. PLoS ONE 8:e70951. doi:10.1371/journal.pone.0070951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Herzog E, Bellenchi GC, Gras C, Bernard V, Ravassard P, Bedet C, Gasnier B, Giros B, El Mestikawy S (2001) The existence of a second vesicular glutamate transporter specifies subpopulations of glutamatergic neurons. J Neurosci 21:RC181

    CAS  PubMed  Google Scholar 

  • Hisano S, Hoshi K, Ikeda Y, Maruyama D, Kanemoto M, Ichijo H, Kojima I, Takeda J, Nogami H (2000) Regional expression of a gene encoding a neuron-specific Na(+)-dependent inorganic phosphate cotransporter (DNPI) in the rat forebrain. Brain Res Mol Brain Res 83:34–43. doi:10.1016/S0169-328X(00)00194-7

    Article  CAS  PubMed  Google Scholar 

  • Izzi L, Lévesque M, Morin S, Laniel D, Wilkes BC, Mille F, Krauss RS, McMahon AP, Allen BL, Charron F (2011) Boc and Gas1 each form distinct Shh receptor complexes with Ptch1 and are required for Shh-mediated cell proliferation. Dev Cell 20:788–801. doi:10.1016/j.devcel.2011.04.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiménez A, López-Ornelas A, Estudillo E, González-Mariscal L, González RO, Segovia J (2014) A soluble form of GAS1 inhibits tumor growth and angiogenesis in a triple negative breast cancer model. Exp Cell Res 327:307–317. doi:10.1016/j.yexcr.2014.06.016

    Article  PubMed  Google Scholar 

  • Kann M, Bae E, Lenz MO, Li L, Trannguyen B, Schumacher VA, Taglienti ME, Bordeianou L, Hartwig S, Rinschen MM, Schermer B, Benzing T, Fan CM, Kreidberg JA (2015) WT1 targets Gas1 to maintain nephron progenitor cells by modulating FGF signals. Development 142:1254–1266. doi:10.1242/dev.119735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaplan MR, Cho MH, Ullian EM, Isom LL, Levinson SR, Barres BA (2001) Differential control of clustering of the sodium channels Na(v)1.2 and Na(v)1.6 at developing CNS nodes of Ranvier. Neuron 30:105–119. doi:10.1016/S0896-6273(01)00266-5

    Article  CAS  PubMed  Google Scholar 

  • Kaufman DL, Houser CR, Tobin AJ (1991) Two forms of the gamma-aminobutyric acid synthetic enzyme glutamate decarboxylase have distinct intraneuronal distributions and cofactor interactions. J Neurochem 56:720–723. doi:10.1111/j.1471-4159.1991.tb08211.x

    Article  CAS  PubMed  Google Scholar 

  • Korecka JA, van Kesteren RE, Blaas E, Spitzer SO, Kamstra JH, Smit AB, Swaab DF, Verhaagen J, Bossers K (2013) Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS ONE 8:e63862. doi:10.1371/journal.pone.0063862

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee CS, Fan CM (2001) Embryonic expression patterns of the mouse and chick Gas1 genes. Mech Dev 101:293–297. doi:10.1016/S0925-4773(01)00283-0

    Article  CAS  PubMed  Google Scholar 

  • Lee CS, Buttitta L, Fan CM (2001a) Evidence that the WNT-inducible growth arrest-specific gene 1 encodes an antagonist of sonic hedgehog signaling in the somite. Proc Nat Acad Sci USA 98:11347–11352. doi:10.1073/pnas.201418298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee KK, Leung AK, Tang MK, Cai DQ, Schneider C, Brancolini C, Chow PH (2001b) Functions of the growth arrest specific 1 gene in the development of the mouse embryo. Dev Biol 234:188–203. doi:10.1006/dbio.2001.0249

    Article  CAS  PubMed  Google Scholar 

  • Leem YE, Han JW, Lee HJ, Ha HL, Kwon YL, Ho SM, Kim BG, Tran P, Bae GU, Kang JS (2011) Gas1 cooperates with Cdo and promotes myogenic differentiation via activation of p38MAPK. Cell Signal 23:2021–2029. doi:10.1016/j.cellsig.2011.07.016

    Article  CAS  PubMed  Google Scholar 

  • Li W, Li K, Wei W, Ding S (2013) Chemical approaches to stem cell biology and therapeutics. Cell Stem Cell 13:270–283. doi:10.1016/j.stem.2013.08.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu Y, May NR, Fan C-M (2001) Growth arrest specific gene 1 is a positive growth regulator for the cerebellum. Dev Biol 236:30–45. doi:10.1006/dbio.2000.0146

    Article  CAS  PubMed  Google Scholar 

  • López-Ornelas A, Mejía-Castillo T, Vergara P, Segovia J (2011) Lentiviral transfer of an inducible transgene expressing a soluble form of Gas1 causes glioma cell arrest, apoptosis and inhibits tumor growth. Cancer Gene Ther 18:87–99. doi:10.1038/cgt.2010.54

    Article  PubMed  Google Scholar 

  • López-Ornelas A, Vergara P, Segovia J (2014) Neural stem cells producing an inducible and soluble form of Gas1 target and inhibit intracranial glioma growth. Cytotherapy 16:1011–1023. doi:10.1016/j.jcyt.2013.12.004

    Article  PubMed  Google Scholar 

  • López-Ramírez MA, Domínguez-Monzón G, Vergara P, Segovia J (2008) Gas1 reduces Ret tyrosine 1062 phosphorylation and alters GDNF-mediated intracellular signaling. Int J Dev Neurosci 26:497–503. doi:10.1016/j.ijdevneu.2008.02.006

    Article  PubMed  Google Scholar 

  • Matas-Rico E, van Veen M, Moolenaar WH (2016) Neuronal differentiation through GPI-anchor cleavage. Cell Cycle 16:388–389. doi:10.1080/15384101.2016.1259894

    Article  PubMed  PubMed Central  Google Scholar 

  • Mellström B, Ceña V, Lamas M, Perales C, Gonzalez C, Naranjo JR (2002) Gas1 is induced during and participates in excitotoxic neuronal death. Mol Cell Neurosci 19:417–429. doi:10.1006/mcne.2001.1092

    Article  PubMed  Google Scholar 

  • Metcalfe C, Bienz M (2011) Inhibition of GSK3 by Wnt signalling–two contrasting models. J Cell Sci 124:3537–3544. doi:10.1242/jcs.091991

    Article  CAS  PubMed  Google Scholar 

  • Muñoz-Montaño JR, Moreno FJ, Avila J, Diaz-Nido J (1997) Lithium inhibits Alzheimer’s disease-like tau protein phosphorylation in neurons. FEBS Lett 411:183–188. doi:10.1016/S0014-5793(97)00688-1

    Article  PubMed  Google Scholar 

  • Muñoz-Montaño JR, Lim F, Moreno FJ, Avila J, Diaz-Nido J (1999a) Glycogen synthase kinase-3 modulates neurite outgrowth in cultured neurons: possible implications for neurite pathology in Alzheimer’s disease. J Alzheimers Dis 1:361–378. doi:10.3233/JAD-1999-1602

    Article  PubMed  Google Scholar 

  • Muñoz-Montaño JR, Moreno FJ, Avila J, Diaz-Nido J (1999b) Downregulation of glycogen synthase kinase-3beta (GSK-3beta) protein expression during neuroblastoma IMR-32 cell differentiation. J Neurosci Res 55:278–285. doi:10.1002/(SICI)1097-4547(19990201)55:3<278:AID-JNR2>3.0.CO;2-2

    Article  PubMed  Google Scholar 

  • Nciri R, Boujbiha MA, Jbahi S, Allagui MS, Elfeki A, Vincent C, Croute F (2015) Cytoskeleton involvement in lithium-induced SH-SY5Y neuritogenesis and the role of glycogen synthase kinase 3beta. Aging Clin Exp Res 27:255–263. doi:10.1007/s40520-014-0290-3

    Article  PubMed  Google Scholar 

  • Paratcha G, Ledda F, Baars L, Coulpier M, Besset V, Anders J, Scott R, Ibáñez CF (2001) Released GFRalpha1 potentiates downstream signaling, neuronal survival, and differentiation via a novel mechanism of recruitment of c-Ret to lipid rafts. Neuron 29:171–184. doi:10.1016/S0896-6273(01)00188-X

    Article  CAS  PubMed  Google Scholar 

  • Ririe KM, Rasmussen RP, Wittwer CT (1997) Product differentiation by analysis of DNA melting curves during the polymerase chain reaction. Anal Biochem 245:154–160. doi:10.1006/abio.1996.9916

    Article  CAS  PubMed  Google Scholar 

  • Rosen CL, Lisanti MP, Salzer JL (1992) Expression of unique sets of GPI-linked proteins by different primary neurons in vitro. J Cell Biol 117:617–627. doi:10.1083/jcb.117.3.617

    Article  CAS  PubMed  Google Scholar 

  • Rougon G, Olive S, Durbec P, Faivre-Sarrailh C, Gennarini G (1994) Functional studies and cellular distribution of the F3 GPI-anchored adhesion molecule. Braz J Med Biol Res 27:409–414

    CAS  PubMed  Google Scholar 

  • Ruaro ME, Stebel M, Vatta P, Marzinotto S, Schneider C (2000) Analysis of the domain requirement in Gas1 growth suppressing activity. FEBS Lett 481:159–163. doi:10.1016/S0014-5793(00)02005-6

    Article  CAS  PubMed  Google Scholar 

  • Sakata-Haga H, Kanemoto M, Maruyama D, Hoshi K, Mogi K, Narita M, Okado N, Ikeda Y, Nogami H, Fukui Y, Kojima I, Takeda J, Hisano S (2001) Differential localization and colocalization of two neuron-types of sodium-dependent inorganic phosphate cotransporters in rat forebrain. Brain Res 902:143–155. doi:10.1016/S0006-8993(01)02290-9

    Article  CAS  PubMed  Google Scholar 

  • Salcedo-Tello P, Ortiz-Matamoros A, Arias C (2011) GSK3 function in the brain during development, neuronal plasticity, and neurodegeneration. Int J Alzheimers Dis 2011:189728. doi:10.4061/2011/189728

    PubMed  PubMed Central  Google Scholar 

  • Schafer MK, Varoqui H, Defamie N, Weihe E, Erickson JD (2002) Molecular cloning and functional identification of mouse vesicular glutamate transporter 3 and its expression in subsets of novel excitatory neurons. J Biol Chem 277:50734–50748. doi:10.1074/jbc.M206738200

    Article  PubMed  Google Scholar 

  • Schneider C, King RM, Philipson L (1988) Genes specifically expressed at growth arrest of mammalian cells. Cell 54:787–793. doi:10.1016/S0092-8674(88)91065-3

    Article  CAS  PubMed  Google Scholar 

  • Schueler-Furman O, Glick E, Segovia J, Linial M (2006) Is GAS1 a co-receptor for the GDNF family of ligands? Trends Pharmacol Sci 27:72–77. doi:10.1016/j.tips.2005.12.004

    Article  CAS  PubMed  Google Scholar 

  • Seppala M, Depew MJ, Martinelli DC, Fan C-M, Sharpe PT, Cobourne MT (2007) Gas1 is a modifier for holoprosencephaly and genetically interacts with sonic hedgehog. J Clin Invest 117:1575–1584. doi:10.1172/jci32032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shah SM, Patel CH, Feng AS, Kollmar R (2013) Lithium alters the morphology of neurites regenerating from cultured adult spiral ganglion neurons. Hear Res 304:137–144. doi:10.1016/j.heares.2013.07.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stebel M, Vatta P, Ruaro ME, Del Sal G, Parton RG, Schneider C (2000) The growth suppressing gas1 product is a GPI-linked protein. FEBS Lett 481:152–158. doi:10.1016/S0014-5793(00)02004-4

    Article  CAS  PubMed  Google Scholar 

  • Sun XL, Chen BY, Zhao HK, Cheng YH, Zheng MH, Duan L, Chen LW (2016) Gas1 up-regulation is inducible and contributes to cell apoptosis in reactive astrocytes in the substantia nigra of LPS and MPTP models. J Neuroinflammation 13:180. doi:10.1186/s12974-016-0643-2

    Article  PubMed  PubMed Central  Google Scholar 

  • Takahashi M, Yasutake K, Tomizawa K (1999) Lithium inhibits neurite growth and tau protein kinase I/glycogen synthase kinase-3beta-dependent phosphorylation of juvenile tau in cultured hippocampal neurons. J Neurochem 73:2073–2083. doi:10.1046/j.1471-4159.1999.02073.x

    CAS  PubMed  Google Scholar 

  • Tamamaki N, Yanagawa Y, Tomioka R, Miyazaki J, Obata K, Kaneko T (2003) Green fluorescent protein expression and colocalization with calretinin, parvalbumin, and somatostatin in the GAD67-GFP knock-in mouse. J Comp Neurol 467:60–79. doi:10.1002/cne.10905

    Article  CAS  PubMed  Google Scholar 

  • Teppola H, Sarkanen JR, Jalonen TO, Linne ML (2016) Morphological differentiation towards neuronal phenotype of SH-SY5Y neuroblastoma cells by estradiol, retinoic acid and cholesterol. Neurochem Res 41:731–747. doi:10.1007/s11064-015-1743-6

    Article  CAS  PubMed  Google Scholar 

  • van Roeyen CR, Zok S, Pruessmeyer J, Boor P, Nagayama Y, Fleckenstein S, Cohen CD, Eitner F, Gröne HJ, Ostendorf T, Ludwig A, Floege J (2013) Growth arrest-specific protein 1 is a novel endogenous inhibitor of glomerular cell activation and proliferation. Kidney Int 83:251–263. doi:10.1038/ki.2012.400

    Article  PubMed  Google Scholar 

  • Varner JA, Emerson DA, Juliano RL (1995) Integrin alpha 5 beta 1 expression negatively regulates cell growth: reversal by attachment to fibronectin. Mol Biol Cell 6:725–740. doi:10.1091/MBC.6.6.725

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Varoqui H, Schafer MK, Zhu H, Weihe E, Erickson JD (2002) Identification of the differentiation-associated Na+/PI transporter as a novel vesicular glutamate transporter expressed in a distinct set of glutamatergic synapses. J Neurosci 22:142–155

    CAS  PubMed  Google Scholar 

  • Wang L, Mear JP, Kuan CY, Colbert MC (2005) Retinoic acid induces CDK inhibitors and growth arrest specific (Gas) genes in neural crest cells. Dev Growth Differ 47:119–130. doi:10.1111/j.1440-169X.2005.00788.x

    Article  CAS  PubMed  Google Scholar 

  • Wang K, Zhu X, Zhang K, Zhou F, Zhu L (2016) Gas1 knockdown increases the neuroprotective effect of glial cell-derived neurotrophic factor against glutamate-induced cell injury in human SH-SY5Y neuroblastoma cells. Cell Mol Neurobiol 36:603–611. doi:10.1007/s10571-015-0241-3

    Article  CAS  PubMed  Google Scholar 

  • Weihe E, Depboylu C, Schütz B, Schäfer MK, Eiden LE (2006) Three types of tyrosine hydroxylase-positive CNS neurons distinguished by dopa decarboxylase and VMAT2 co-expression. Cell Mol Neurobiol 26:657–676

    Article  Google Scholar 

  • Zarco N, González-Ramírez R, González RO, Segovia J (2012) GAS1 induces cell death through an intrinsic apoptotic pathway. Apoptosis 17:627–635. doi:10.1007/s10495-011-0696-8

    Article  CAS  PubMed  Google Scholar 

  • Zarco N, Bautista E, Cuéllar M, Vergara P, Flores-Rodriguez P, Aguilar-Roblero R, Segovia J (2013) Growth arrest specific 1 (GAS1) is abundantly expressed in the adult mouse central nervous system. J Histochem Cytochem 61:731–748. doi:10.1369/0022155413498088

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang W, Smith A, Liu JP, Cheung NS, Zhou S, Liu K, Li QT, Duan W (2009) GSK3beta modulates PACAP-induced neuritogenesis in PC12 cells by acting downstream of Rap1 in a caveolae-dependent manner. Cell Signal 21:237–245. doi:10.1016/j.cellsig.2008.10.008

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This study was partially supported by CONACyT (Mexico) Grants 239516 (JS) and PAPIIT/DGAPA IN205917 (R.A.-R.). The authors wish to thank Araceli Navarrete Alonso for their technical support and Rubén Sánchez for his laboratory assistance.

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Authors and Affiliations

  1. Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, Av. IPN # 2508, 07300, Mexico, DF, Mexico

    Elizabeth Bautista, Natanael Zarco, Nicolás Aguirre-Pineda, Manuel Lara-Lozano, Paula Vergara & José Segovia

  2. Laboratorio de Medicina Genómica, Hospital Regional 1 de Octubre, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE), Avenida Instituto Politécnico Nacional N° 1669, Gustavo A. Madero, Col. Magdalena de las Salinas, Del. Gustavo A. Madero, 07760, Mexico, DF, Mexico

    Manuel Lara-Lozano & Juan Antonio González-Barrios

  3. Departamento de Neurociencia Cognitiva, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Ciudad Universitaria, Coyoacan, 04510, Mexico, DF, Mexico

    Raúl Aguilar-Roblero

Authors
  1. Elizabeth Bautista
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  2. Natanael Zarco
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  3. Nicolás Aguirre-Pineda
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  4. Manuel Lara-Lozano
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  5. Paula Vergara
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  6. Juan Antonio González-Barrios
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  7. Raúl Aguilar-Roblero
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  8. José Segovia
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Contributions

Designed research: EB, NZ, MLL, and JS; performed research: EB, MLL, NZ, NA-P, and PV; analyzed data: JAGB, EB, RAR, and JS; wrote the manuscript: EB and JS.

Corresponding author

Correspondence to José Segovia.

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Conflict of interest

The authors declare no competing financial interests nor other potential conflicts of interest.

Ethical Approval

Experiments were performed according to the current Mexican legislation NOM-062-ZOO-1999 (SAGARPA) and internal institutional guidelines, per authorization 0152-03, from Cinvestav (Comité Interno para el Cuidado y Uso de Animales de Laboratorio).

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Fig. 1

Gas1 is expressed in the (A–C) cerebellar cortex (D–F) medulla oblongata and (G–I) cortex of the adult mouse brain. Bar: (A and D) 100 μm. (TIFF 237 kb)

Supplementary Fig. 2

Levels of gas1 mRNA from different brain regions, as determined by RT-PCR. B (-) no cDNA added; NP, proliferating NIH/3T3 cells; N24, arrested NIH/3T3 cells; Cb, cerebellum; Hip, hippocampus; Tal, Thalamus (TIFF 23 kb)

Supplementary Fig. 3

Gas1 co-localizes with GAD67 and VGLUT2 in hippocampus CA1. (A-B) Gas1 (green) is present in the soma of GABAergic neurons (GAD67 +: red) of the stratum oriens and (D-E) in the soma of glutamatergic neurons (VGLUT2+: red) of hippocampal CA1 pyramidal cells. Nuclei were counterstained with DAPI (blue). Cells indicated by arrows in A and D, are amplified in B and D, respectively. Bar: (A and D) 100 μm, (B and E) 10 μm. C and F represent the areas examined. Abbreviations are expounded in Table 1 (TIFF 211 kb)

Supplementary Fig. 4

Gas1 is expressed in GABAergic and glutamatergic neurons of hippocampus CA2. (A-B) Gas1 (green) is present in the soma of GABAergic neurons (GAD67 +: red) of stratum oriens and (D-E) in the soma of glutamatergic neurons (VGLUT2+: red) of hippocampal CA2 pyramidal cells. Nuclei were counterstained with DAPI (blue). Cells indicated by arrows in A and D, are amplified in B and E, respectively. Bar: (A and D) 100 μm, (B and E) 10 μm. C and F show the areas examined. Abbreviations are expound in Table 1 (TIFF 245 kb)

Supplementary Fig. 5

Gas1 is expressed in GABAergic neurons of the molecular layer of the hippocampus. (A-B) Gas1 (green) is present in the soma of GABAergic neurons (GAD67 +: red) of the molecular layer but not (D-E) in the GABAergic neuropil of the CA2 pyramidal layer. Nuclei were counterstained with DAPI (blue). Cell indicated by arrow in A is amplified in B; the inset in B is amplified in E. Bar: (A and D) 100 μm, (B and E) 10 μm. C and F show the areas examined. Abbreviations are expounded in Table 1 (TIFF 245 kb)

Supplementary Fig. 6

Effect of Gas1 on cell viability. SH-SY5Y cells were cultured for 7 days in the presence of AR with different concentration of rh_Gas1. Mitochondrial activity was determined by the MTT assay and is expressed as percentage of viable cells. We used one-way ANOVA followed by Tukey´s post hoc multiple comparison test. Bars are mean ± SEM (n = 3). There were no significant differences among groups (TIFF 39 kb)

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Bautista, E., Zarco, N., Aguirre-Pineda, N. et al. Expression of Gas1 in Mouse Brain: Release and Role in Neuronal Differentiation. Cell Mol Neurobiol 38, 841–859 (2018). https://doi.org/10.1007/s10571-017-0559-0

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