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Pnn and SR family proteins are differentially expressed in mouse central nervous system

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Abstract

Pinin (pnn) is an SR-related protein that is ubiquitously expressed in most cell types and functions in regulating pre-mRNA splicing and mRNA export. Previously, we demonstrated that pnn is expressed in all tissues during mouse embryonic development with highest levels of expression in the central nervous system (CNS). Here we show that pnn and other SR proteins including SC35 are differentially expressed in the adult mouse CNS, displaying cell type-specific distribution patterns. Immunohistochemical analysis of whole-brain sections showed that levels of pnn and SR proteins expression were very low or nonexistent in the corpus callosum and white matter of cerebellum and spinal cord. Double-immunostaining with antibodies specific to neuron or glial cells showed that most astrocytes and microglia expressed neither pnn nor SR proteins. In contrast, oligodendrocytes and neurons expressed moderate and high levels, respectively, of both pnn and SR proteins. These results suggest that astrocytes are unique among cell types of neuroblast origin in terms of expression SR family proteins. Our results pave the way for future studies of the functional roles of pnn and SR family proteins in adults.

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References

  • Black DL (2003) Mechanisms of alternative pre-messenger RNA splicing. Annu Rev Biochem 72:291–336

    Article  PubMed  CAS  Google Scholar 

  • Brandner JM, Reidenbach S, Franke WW (1997) Evidence that “pinin”, reportedly a differentiation-specific desmosomal protein, is actually a widespread nuclear protein. Differentiation 62:119–127

    Article  PubMed  CAS  Google Scholar 

  • Brandner JM, Reidenbach S, Kuhn C, Franke WW (1998) Identification and characterization of a novel kind of nuclear protein occurring free in the nucleoplasm and in ribonucleoprotein structures of the “speckle” type. Eur J Cell Biol 75:295–308

    PubMed  CAS  Google Scholar 

  • Chandra S, Deikus G, Tardos JG, Bogdanov VY (2010) Antagonistic roles of four SR proteins in the biosynthesis of alternatively spliced tissue factor transcripts in monocytic cells. J Leukoc Biol 87:147–152

    Article  Google Scholar 

  • Confaloni A, Crestini A, Albani D, Piscopo P, Campeggi LM, Terreni L, Tartaglia M, Forloni G (2005) Rat nicastrin gene: cDNA isolation, mRNA variants and expression pattern analysis. Mol Brain Res 136:12–22

    Article  PubMed  CAS  Google Scholar 

  • Ding JH, Xu X, Yang D, Chu PH, Dalton ND, Ye Z, Yeakley JM, Cheng H, Xiao RP, Ross J Jr, Chen J, Fu XD (2004) Dilated cardiomyopathy caused by tissue-specific ablation of SC35 in the heart. EMBO J 23:885–896

    Article  PubMed  CAS  Google Scholar 

  • Dowling D, Nasr-Esfahani S, Tan CH, O’Brien K, Howard JL, Jans DA, Purcell DFJ, Stolzfus CM, Sonza S (2008) HIV-1 infection induces changes in expression of cellular splicing factors that regulate alternative viral splicing and virus production in macrophages. Retrovirology 5:18–29

    Article  PubMed  Google Scholar 

  • Emery B (2010) Regulation of oligodendrocyte differentiation and myelination. Science 330:779–782

    Article  PubMed  CAS  Google Scholar 

  • Fang Y, Searn S, Spector DL (2004) Tissue-specific expression and dynamic organization of SR splicing factors in Arabidopsis. Mol Biol Cell 15:2664–2673

    Article  PubMed  CAS  Google Scholar 

  • Freeman MR (2010) Specification and morphogenesis of astrocytes. Science 330:774–778

    Article  PubMed  CAS  Google Scholar 

  • Gao L, Wang J, Wang Y, Andreadis A (2007) SR protein 9G8 modulates splicing of tau exon 10 via its proximal downstream intron, a clustering region for frontotemporal dementia mutations. Mol Cell Neurosci 34:48–58

    Article  PubMed  CAS  Google Scholar 

  • Grabowski PJ, Black DL (2001) Alternative RNA splicing in the nervous system. Prog Neurobiol 65:289–308

    Article  PubMed  CAS  Google Scholar 

  • Hanamura A, Caceres JF, Mayeda A, Franza BR Jr, Krainer AR (1998) Regulated tissue-specific expression of antagonistic pre-mRNA splicing factors. RNA 4:430–444

    PubMed  CAS  Google Scholar 

  • Hofmann Y, Lorson CL, Stamm S, Androphy EJ, Wirth B (2000) Htra2-β1 stimulates an exonic splicing enhancer and can restore full-length SMN expression to survival motor neuron 2 (SMN2). Proc Natl Acad Sci USA 97:9618–9623

    Article  PubMed  CAS  Google Scholar 

  • Hubner S, Jans DA, Drenckhahn D (2001) Roles of cytoskeletal and junctional plaque proteins in nuclear signaling. Int Rev Cytol 208:207–265

    Article  PubMed  CAS  Google Scholar 

  • Joo JH, Alpatov R, Munguba GC, Jackson MR, Hunt ME, Sugrue S (2005) Reduction of Pnn by RNAi induces loss of cell-cell adhesion between human corneal epithelial cells. Mol Vis 11:133–142

    PubMed  CAS  Google Scholar 

  • Joo JH, Kim YH, Munguba GC, Dunn NW, Sugrue S (2010a) Disruption of mouse corneal epithelial differentiation by conditional inactivation of Pnn. Invest Ophthalmol Vis Sci 51:1927–1934

    Article  PubMed  Google Scholar 

  • Joo JH, Lee YJ, Taxter TJ, Munguba GC, Kim YH, Dhaduvai K, Dunn NW, Degan WJ, Oh SP, Sugrue S (2010b) Pinin modulates expression of an intestinal homeobox gene, Cdx2, and plays an essential role for small intestinal morphology. Dev Biol 345:191–203

    Article  PubMed  CAS  Google Scholar 

  • Katsu R, Onogi H, Wada K, Kawaguchi Y, Hagiwara M (2002) Novel SR-rich-related protein clasp specifically interacts with inactivated Clk4 and induces the exon EB inclusion of Clk. J Biol Chem 277:44220–44228

    Article  PubMed  CAS  Google Scholar 

  • Lee A, Pow DV (2010) Astrocytes: glutamate transport and alternative splicing of transporters. Int J Biochem Cell Biol 42:1901–1906

    Article  PubMed  CAS  Google Scholar 

  • Leu S, Ouyang P (2006) Spatial and temporal expression profiles of Pinin during mouse development. Gene Exp Pattern 6:620–631

    Article  CAS  Google Scholar 

  • Li C, Lin RI, Lai MC, Ouyang P, Tarn WY (2003) Nuclear Pnn/DRS protein binds to spliced mRNPs and participates in mRNA processing and export via interaction with RNPS1. Mol Cell Biol 23:7363–7376

    Article  PubMed  CAS  Google Scholar 

  • Lin CL, Leu S, Lu MC, Ouyang P (2004) Over-expression of SR-cyclophilin, an interaction partner of nuclear pinin, releases SR family splicing factors from nuclear speckles. Biochem Biophys Res Commun 321:638–647

    Article  PubMed  CAS  Google Scholar 

  • Meshoere E, Bryk B, Toiber D, Cohen J, Podoly E, Dori A, Soreq H (2005) SC35 promotes sustainable stress-induced alternative splicing of neuronal acetylcholinesterase mRNA. Mol Psychiatry 10:985–997

    Article  Google Scholar 

  • Möröy T, Heyd F (2007) The impact of alternative splicing in vivo: mouse models show the way. RNA 13:1155–1171

    Article  PubMed  Google Scholar 

  • Nielson JA, Hudson LD, Armstrong RC (2002) Nuclear organization in differentiating oligodendrocytes. J Cell Sci 115:4071–4079

    Article  Google Scholar 

  • Ouyang P (1999) Antibodies differentiate desmosome-form and nucleus-form pinin: evidence that pinin is a moonlighting protein with dual location at the desmosome and within the nucleus. Biochem Biophys Res Commun 263:192–200

    Article  PubMed  CAS  Google Scholar 

  • Ouyang P, Sugrue SP (1992) Identification of an epithelial protein related to the desmosome and intermediate filament network. J Cell Biol 118:1477–1488

    Article  PubMed  CAS  Google Scholar 

  • Ouyang P, Sugrue SP (1996) Characterization of pinin, a novel protein associated with the desmosome-intermediate filament complex. J Cell Biol 135:1027–1042

    Article  PubMed  CAS  Google Scholar 

  • Ouyang P, Zhen YY, Sugrue SP (1997) Cloning and analysis of cDNA encoding murine pinin. Gene 197:115–120

    Article  PubMed  CAS  Google Scholar 

  • Paus T, Zijdenbos A, Worsley K, Collins DL, Blumenthal J, Giedd JN, Rapoport JL, Evans AC (1999) Structural maturation of neural pathways in children and adolescents: in vivo study. Science 283:1908–1911

    Article  PubMed  CAS  Google Scholar 

  • Richardson WD, Kessaris N, Pringle N (2006) Oligodendrocyte wars. Nat Rev Neurosci 7:11–18

    Article  PubMed  CAS  Google Scholar 

  • Sakashita E, Tatsumi S, Werner D, Endo H, Mayeda A (2004) Human RNPS1 and its associated factors: a versatile alternative pre-mRNA splicing regulator in vivo. Mol Cell Biol 24:1174–1187

    Article  PubMed  CAS  Google Scholar 

  • Shi Y, Tabesh M, Sugrue SP (2000) Role of cell adhesion-associated protein, pinin (DRS/memA), in corneal epithelial migration. Invest Ophthalmol Vis Sci 41:1337–1345

    PubMed  CAS  Google Scholar 

  • Shi Y, Simmons MN, Seki T, Oh SP, Sugrue SP (2001) Change in gene expression subsequent to induction of Pnn/DRS/memA: increase in p21(cip1/waf1). Oncogene 20:4007–4018

    Article  PubMed  CAS  Google Scholar 

  • Ulfig N, Briese V (1999) Immunolabelling of spliceosomes in sections and cultured astrocytes of human fetal brain tissue. Brain Dev 21:51–58

    Article  PubMed  CAS  Google Scholar 

  • Wang P, Lou PJ, Leu S, Ouyang P (2002) Modulation of alterative pre-mRNA splicing in vivo by pinin. Biochem Biophys Res Commun 294:448–455

    Article  PubMed  CAS  Google Scholar 

  • Xu X, Yang D, Ding JH, Wang W, Chu PH, Dalton ND, Wang HY, Bermingham JR Jr, Ye Z, Liu F, Rosenfeld MG, Manley JL, Ross J Jr, Chen J, Xiao RP, Cheng H, Fu XD (2005) ASF/SF2-regulated CaMKIIdelta alternative splicing temporally reprograms excitation–contraction coupling in cardiac muscle. Cell 120:59–72

    Article  PubMed  CAS  Google Scholar 

  • Young PJ, DiDonato CJ, Hu D, Kothary R, Androphy EJ, Lorson CL (2002) SRp30c-dependent stimulation of survival motor neuron (SMN) exon 7 inclusion is facilitated by a direct interaction with hTra2β1. Hum Mol Genet 11:577–587

    Article  PubMed  CAS  Google Scholar 

  • Zimowska G, Shi J, Munguba G, Jackson MR, Alpatov R, Simmons MN, Shi Y, Sugrue SP (2003) Pinin/DRS/memA interacts with SRp75, SRm300 and SRrp130 in corneal epithelial cells. Invest Ophthalmol Vis Sci 44:4715–4723

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from Chang Gung Memorial Hospital (CMRPD 170073), the Ministry of Education (EMRPD 190481) and the National Science Council, ROC (NSC-98-2320-B-182-019-MY3).

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Correspondence to Pin Ouyang.

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Hsu, SY., Chen, YJ. & Ouyang, P. Pnn and SR family proteins are differentially expressed in mouse central nervous system. Histochem Cell Biol 135, 361–373 (2011). https://doi.org/10.1007/s00418-011-0795-1

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