Human PDCD2L Is an Export Substrate of CRM1 That Associates with 40S Ribosomal Subunit Precursors

REFERENCES

• Woolford JL, Jr, Baserga SJ. 2013. Ribosome biogenesis in the yeast Saccharomyces cerevisiae. Genetics 195:643–681. http://dx.doi.org/10.1534/genetics.113.153197.
   PubMed Web of Science ®Google Scholar
• Kusnadi EP, Hannan KM, Hicks RJ, Hannan RD, Pearson RB, Kang J. 2015. Regulation of rDNA transcription in response to growth factors, nutrients and energy. Gene 556:27–34. http://dx.doi.org/10.1016/j.gene.2014.11.010.
   PubMed Web of Science ®Google Scholar
• Sanchez CG, Teixeira FK, Czech B, Preall JB, Zamparini AL, Seifert JR, Malone CD, Hannon GJ, Lehmann R. 2016. Regulation of ribosome biogenesis and protein synthesis controls germline stem cell differentiation. Cell Stem Cell 18:276–290. http://dx.doi.org/10.1016/j.stem.2015.11.004.
   PubMed Web of Science ®Google Scholar
• Zhang Q, Shalaby NA, Buszczak M. 2014. Changes in rRNA transcription influence proliferation and cell fate within a stem cell lineage. Science 343:298–301. http://dx.doi.org/10.1126/science.1246384.
   PubMedGoogle Scholar
• Gentilella A, Kozma SC, Thomas G. 2015. A liaison between mTOR signaling, ribosome biogenesis and cancer. Biochim Biophys Acta 1849:812–820. http://dx.doi.org/10.1016/j.bbagrm.2015.02.005.
   PubMed Web of Science ®Google Scholar
• Henras AK, Plisson-Chastang C, O'Donohue MF, Chakraborty A, Gleizes PE. 2015. An overview of pre-ribosomal RNA processing in eukaryotes. Wiley Interdiscip Rev RNA 6:225–242. http://dx.doi.org/10.1002/wrna.1269.
   PubMed Web of Science ®Google Scholar
• Nerurkar P, Altvater M, Gerhardy S, Schutz S, Fischer U, Weirich C, Panse VG. 2015. Eukaryotic ribosome assembly and nuclear export. Int Rev Cell Mol Biol 319:107–140. http://dx.doi.org/10.1016/bs.ircmb.2015.07.002.
   PubMed Web of Science ®Google Scholar
• Gadal O, Strauss D, Kessl J, Trumpower B, Tollervey D, Hurt E. 2001. Nuclear export of 60S ribosomal subunits depends on Xpo1p and requires a nuclear export sequence-containing factor, Nmd3p, that associates with the large subunit protein Rpl10p. Mol Cell Biol 21:3405–3415. http://dx.doi.org/10.1128/MCB.21.10.3405-3415.2001.
   PubMed Web of Science ®Google Scholar
• Ho JH, Kallstrom G, Johnson AW. 2000. Nmd3p is a Crm1p-dependent adapter protein for nuclear export of the large ribosomal subunit. J Cell Biol 151:1057–1066. http://dx.doi.org/10.1083/jcb.151.5.1057.
   PubMed Web of Science ®Google Scholar
• Thomas F, Kutay U. 2003. Biogenesis and nuclear export of ribosomal subunits in higher eukaryotes depend on the CRM1 export pathway. J Cell Sci 116:2409–2419. http://dx.doi.org/10.1242/jcs.00464.
   PubMedGoogle Scholar
• Trotta CR, Lund E, Kahan L, Johnson AW, Dahlberg JE. 2003. Coordinated nuclear export of 60S ribosomal subunits and NMD3 in vertebrates. EMBO J 22:2841–2851. http://dx.doi.org/10.1093/emboj/cdg249.
   PubMedGoogle Scholar
• Xue S, Barna M. 2012. Specialized ribosomes: a new frontier in gene regulation and organismal biology. Nat Rev Mol Cell Biol 13:355–369. http://dx.doi.org/10.1038/nrm3359.
   PubMed Web of Science ®Google Scholar
• Lee SW, Berger SJ, Martinovic S, Pasa-Tolic L, Anderson GA, Shen Y, Zhao R, Smith RD. 2002. Direct mass spectrometric analysis of intact proteins of the yeast large ribosomal subunit using capillary LC/FTICR. Proc Natl Acad Sci U S A 99:5942–5947. http://dx.doi.org/10.1073/pnas.082119899.
   PubMed Web of Science ®Google Scholar
• Louie DF, Resing KA, Lewis TS, Ahn NG. 1996. Mass spectrometric analysis of 40 S ribosomal proteins from Rat-1 fibroblasts. J Biol Chem 271:28189–28198. http://dx.doi.org/10.1074/jbc.271.45.28189.
   PubMedGoogle Scholar
• Odintsova TI, Muller EC, Ivanov AV, Egorov TA, Bienert R, Vladimirov SN, Kostka S, Otto A, Wittmann-Liebold B, Karpova GG. 2003. Characterization and analysis of posttranslational modifications of the human large cytoplasmic ribosomal subunit proteins by mass spectrometry and Edman sequencing. J Protein Chem 22:249–258. http://dx.doi.org/10.1023/A:1025068419698.
   PubMedGoogle Scholar
• Kruiswijk T, Kunst A, Planta RJ, Mager WH. 1978. Modification of yeast ribosomal proteins. Methylation Biochem J 175:221–225.
   PubMedGoogle Scholar
• Lhoest J, Lobet Y, Costers E, Colson C. 1984. Methylated proteins and amino acids in the ribosomes of Saccharomyces cerevisiae. Eur J Biochem 141:585–590. http://dx.doi.org/10.1111/j.1432-1033.1984.tb08233.x.
   PubMedGoogle Scholar
• Ramagopal S. 1991. Covalent modifications of ribosomal proteins in growing and aggregation-competent Dictyostelium discoideum: phosphorylation and methylation. Biochem Cell Biol 69:263–268. http://dx.doi.org/10.1139/o91-040.
   PubMedGoogle Scholar
• Chang FN, Navickas IJ, Au C, Budzilowicz C. 1978. Identification of the methylated ribosomal proteins in HeLa cells and the fluctuation of methylation during the cell cycle. Biochim Biophys Acta 518:89–94. http://dx.doi.org/10.1016/0005-2787(78)90118-1.
   PubMedGoogle Scholar
• Yu Y, Ji H, Doudna JA, Leary JA. 2005. Mass spectrometric analysis of the human 40S ribosomal subunit: native and HCV IRES-bound complexes. Protein Sci 14:1438–1446.
   PubMed Web of Science ®Google Scholar
• Bachand F, Silver PA. 2004. PRMT3 is a ribosomal protein methyltransferase that affects the cellular levels of ribosomal subunits. EMBO J 23:2641–2650. http://dx.doi.org/10.1038/sj.emboj.7600265.
   PubMed Web of Science ®Google Scholar
• Bachand F. 2007. Protein arginine methyltransferases: from unicellular eukaryotes to humans. Eukaryot Cell 6:889–898. http://dx.doi.org/10.1128/EC.00099-07.
   PubMedGoogle Scholar
• Perreault A, Gascon S, D'Amours A, Aletta JM, Bachand F. 2009. A methyltransferase-independent function for Rmt3 in ribosomal subunit homeostasis. J Biol Chem 284:15026–15037. http://dx.doi.org/10.1074/jbc.M109.004812.
   PubMedGoogle Scholar
• Swiercz R, Person MD, Bedford MT. 2005. Ribosomal protein S2 is a substrate for mammalian PRMT3 (protein arginine methyltransferase 3). Biochem J 386:85–91. http://dx.doi.org/10.1042/BJ20041466.
   PubMed Web of Science ®Google Scholar
• Lipson RS, Webb KJ, Clarke SG. 2010. Rmt1 catalyzes zinc-finger independent arginine methylation of ribosomal protein Rps2 in Saccharomyces cerevisiae. Biochem Biophys Res Commun 391:1658–1662. http://dx.doi.org/10.1016/j.bbrc.2009.12.112.
   PubMed Web of Science ®Google Scholar
• Hang R, Liu C, Ahmad A, Zhang Y, Lu F, Cao X. 2014. Arabidopsis protein arginine methyltransferase 3 is required for ribosome biogenesis by affecting precursor ribosomal RNA processing. Proc Natl Acad Sci U S A 111:16190–16195. http://dx.doi.org/10.1073/pnas.1412697111.
   PubMedGoogle Scholar
• Swiercz R, Cheng D, Kim D, Bedford MT. 2007. Ribosomal protein rpS2 is hypomethylated in PRMT3-deficient mice. J Biol Chem 282:16917–16923. http://dx.doi.org/10.1074/jbc.M609778200.
   PubMed Web of Science ®Google Scholar
• Burroughs AM, Aravind L. 2014. Analysis of two domains with novel RNA-processing activities throws light on the complex evolution of ribosomal RNA biogenesis. Front Genet 5:424. http://dx.doi.org/10.3389/fgene.2014.00424.
   PubMed Web of Science ®Google Scholar
• Li Z, Lee I, Moradi E, Hung NJ, Johnson AW, Marcotte EM. 2009. Rational extension of the ribosome biogenesis pathway using network-guided genetics. PLoS Biol 7:e1000213. http://dx.doi.org/10.1371/journal.pbio.1000213.
   PubMed Web of Science ®Google Scholar
• Bergeron D, Pal G, Beaulieu YB, Chabot B, Bachand F. 2015. Regulated intron retention and nuclear pre-mRNA decay contribute to PABPN1 autoregulation. Mol Cell Biol 35:2503–2517. http://dx.doi.org/10.1128/MCB.00070-15.
   PubMed Web of Science ®Google Scholar
• Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA, Zhang F. 2013. Genome engineering using the CRISPR-Cas9 system. Nat Protoc 8:2281–2308. http://dx.doi.org/10.1038/nprot.2013.143.
   PubMed Web of Science ®Google Scholar
• Drissi R, Dubois ML, Douziech M, Boisvert FM. 2015. Quantitative proteomics reveals dynamic interactions of the minichromosome maintenance complex (MCM) in the cellular response to etoposide induced DNA damage. Mol Cell Proteomics 14:2002–2013. http://dx.doi.org/10.1074/mcp.M115.048991.
   PubMed Web of Science ®Google Scholar
• Bachand F, Yao XJ, Hrimech M, Rougeau N, Cohen EA. 1999. Incorporation of Vpr into human immunodeficiency virus type 1 requires a direct interaction with the p6 domain of the p55 gag precursor. J Biol Chem 274:9083–9091. http://dx.doi.org/10.1074/jbc.274.13.9083.
   PubMedGoogle Scholar
• Carron C, O'Donohue MF, Choesmel V, Faubladier M, Gleizes PE. 2011. Analysis of two human pre-ribosomal factors, bystin and hTsr1, highlights differences in evolution of ribosome biogenesis between yeast and mammals. Nucleic Acids Res 39:280–291. http://dx.doi.org/10.1093/nar/gkq734.
   PubMed Web of Science ®Google Scholar
• Choesmel V, Fribourg S, Aguissa-Toure AH, Pinaud N, Legrand P, Gazda HT, Gleizes PE. 2008. Mutation of ribosomal protein RPS24 in Diamond-Blackfan anemia results in a ribosome biogenesis disorder. Hum Mol Genet 17:1253–1263. http://dx.doi.org/10.1093/hmg/ddn015.
   PubMed Web of Science ®Google Scholar
• Mallet PL, Bachand F. 2013. A proline-tyrosine nuclear localization signal (PY-NLS) is required for the nuclear import of fission yeast PAB2, but not of human PABPN1. Traffic 14:282–294. http://dx.doi.org/10.1111/tra.12036.
   PubMedGoogle Scholar
• Port SA, Monecke T, Dickmanns A, Spillner C, Hofele R, Urlaub H, Ficner R, Kehlenbach RH. 2015. Structural and functional characterization of CRM1-Nup214 interactions reveals multiple FG-binding sites involved in nuclear export. Cell Rep 13:690–702. http://dx.doi.org/10.1016/j.celrep.2015.09.042.
   PubMedGoogle Scholar
• Ong SE, Blagoev B, Kratchmarova I, Kristensen DB, Steen H, Pandey A, Mann M. 2002. Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol Cell Proteomics 1:376–386. http://dx.doi.org/10.1074/mcp.M200025-MCP200.
   PubMed Web of Science ®Google Scholar
• Giot L, Bader JS, Brouwer C, Chaudhuri A, Kuang B, Li Y, Hao YL, Ooi CE, Godwin B, Vitols E, Vijayadamodar G, Pochart P, Machineni H, Welsh M, Kong Y, Zerhusen B, Malcolm R, Varrone Z, Collis A, Minto M, Burgess S, McDaniel L, Stimpson E, Spriggs F, Williams J, Neurath K, Ioime N, Agee M, Voss E, Furtak K, Renzulli R, Aanensen N, Carrolla S, Bickelhaupt E, Lazovatsky Y, DaSilva A, Zhong J, Stanyon CA, Finley RL, Jr, White KP, Braverman M, Jarvie T, Gold S, Leach M, Knight J, Shimkets RA, McKenna MP, Chant J, Rothberg JM. 2003. A protein interaction map of Drosophila melanogaster. Science 302:1727–1736. http://dx.doi.org/10.1126/science.1090289.
   PubMed Web of Science ®Google Scholar
• Schafer T, Strauss D, Petfalski E, Tollervey D, Hurt E. 2003. The path from nucleolar 90S to cytoplasmic 40S pre-ribosomes. EMBO J 22:1370–1380. http://dx.doi.org/10.1093/emboj/cdg121.
   PubMed Web of Science ®Google Scholar
• Wyler E, Zimmermann M, Widmann B, Gstaiger M, Pfannstiel J, Kutay U, Zemp I. 2011. Tandem affinity purification combined with inducible shRNA expression as a tool to study the maturation of macromolecular assemblies. RNA 17:189–200. http://dx.doi.org/10.1261/rna.2325911.
   PubMed Web of Science ®Google Scholar
• Zemp I, Wild T, O'Donohue MF, Wandrey F, Widmann B, Gleizes PE, Kutay U. 2009. Distinct cytoplasmic maturation steps of 40S ribosomal subunit precursors require hRio2. J Cell Biol 185:1167–1180. http://dx.doi.org/10.1083/jcb.200904048.
   PubMed Web of Science ®Google Scholar
• Rouquette J, Choesmel V, Gleizes PE. 2005. Nuclear export and cytoplasmic processing of precursors to the 40S ribosomal subunits in mammalian cells. EMBO J 24:2862–2872. http://dx.doi.org/10.1038/sj.emboj.7600752.
   PubMed Web of Science ®Google Scholar
• Kirli K, Karaca S, Dehne HJ, Samwer M, Pan KT, Lenz C, Urlaub H, Gorlich D. 2015. A deep proteomics perspective on CRM1-mediated nuclear export and nucleocytoplasmic partitioning. eLife 4:e11466. http://dx.doi.org/10.7554/eLife.11466.
   PubMed Web of Science ®Google Scholar
• Thakar K, Karaca S, Port SA, Urlaub H, Kehlenbach RH. 2013. Identification of CRM1-dependent nuclear export cargos using quantitative mass spectrometry. Mol Cell Proteomics 12:664–678. http://dx.doi.org/10.1074/mcp.M112.024877.
   PubMed Web of Science ®Google Scholar
• Kudo N, Matsumori N, Taoka H, Fujiwara D, Schreiner EP, Wolff B, Yoshida M, Horinouchi S. 1999. Leptomycin B inactivates CRM1/exportin 1 by covalent modification at a cysteine residue in the central conserved region. Proc Natl Acad Sci U S A 96:9112–9117. http://dx.doi.org/10.1073/pnas.96.16.9112.
   PubMed Web of Science ®Google Scholar
• Fu SC, Imai K, Horton P. 2011. Prediction of leucine-rich nuclear export signal containing proteins with NESsential. Nucleic Acids Res 39:e111. http://dx.doi.org/10.1093/nar/gkr493.
   PubMedGoogle Scholar
• la Cour T, Kiemer L, Molgaard A, Gupta R, Skriver K, Brunak S. 2004. Analysis and prediction of leucine-rich nuclear export signals. Protein Eng Des Sel 17:527–536. http://dx.doi.org/10.1093/protein/gzh062.
   PubMed Web of Science ®Google Scholar
• Kutay U, Guttinger S. 2005. Leucine-rich nuclear-export signals: born to be weak. Trends Cell Biol 15:121–124. http://dx.doi.org/10.1016/j.tcb.2005.01.005.
   PubMed Web of Science ®Google Scholar
• Meyer BE, Malim MH. 1994. The HIV-1 Rev trans-activator shuttles between the nucleus and the cytoplasm. Genes Dev 8:1538–1547. http://dx.doi.org/10.1101/gad.8.13.1538.
   PubMedGoogle Scholar
• Boisvert FM, Lam YW, Lamont D, Lamond AI. 2010. A quantitative proteomics analysis of subcellular proteome localization and changes induced by DNA damage. Mol Cell Proteomics 9:457–470. http://dx.doi.org/10.1074/mcp.M900429-MCP200.
   PubMed Web of Science ®Google Scholar
• Minakhina S, Naryshkina T, Changela N, Tan W, Steward R. 2016. Zfrp8/PDCD2 interacts with RpS2 connecting ribosome maturation and gene-specific translation. PLoS One 11:e0147631. http://dx.doi.org/10.1371/journal.pone.0147631.
   PubMedGoogle Scholar
• Huttlin EL, Ting L, Bruckner RJ, Gebreab F, Gygi MP, Szpyt J, Tam S, Zarraga G, Colby G, Baltier K, Dong R, Guarani V, Vaites LP, Ordureau A, Rad R, Erickson BK, Wuhr M, Chick J, Zhai B, Kolippakkam D, Mintseris J, Obar RA, Harris T, Artavanis-Tsakonas S, Sowa ME, De Camilli P, Paulo JA, Harper JW, Gygi SP. 2015. The BioPlex network: a systematic exploration of the human interactome. Cell 162:425–440. http://dx.doi.org/10.1016/j.cell.2015.06.043.
   PubMed Web of Science ®Google Scholar
• Bhavsar RB, Makley LN, Tsonis PA. 2010. The other lives of ribosomal proteins. Hum Genomics 4:327–344. http://dx.doi.org/10.1186/1479-7364-4-5-327.
   PubMedGoogle Scholar
• Lu H, Zhu YF, Xiong J, Wang R, Jia Z. 2015. Potential extra-ribosomal functions of ribosomal proteins in Saccharomyces cerevisiae. Microbiol Res 177:28–33. http://dx.doi.org/10.1016/j.micres.2015.05.004.
   PubMedGoogle Scholar
• Warner JR, McIntosh KB. 2009. How common are extraribosomal functions of ribosomal proteins? Mol Cell 34:3–11. http://dx.doi.org/10.1016/j.molcel.2009.03.006.
   PubMed Web of Science ®Google Scholar
• Ferreira-Cerca S, Poll G, Gleizes PE, Tschochner H, Milkereit P. 2005. Roles of eukaryotic ribosomal proteins in maturation and transport of pre-18S rRNA and ribosome function. Mol Cell 20:263–275. http://dx.doi.org/10.1016/j.molcel.2005.09.005.
   PubMed Web of Science ®Google Scholar
• O'Donohue MF, Choesmel V, Faubladier M, Fichant G, Gleizes PE. 2010. Functional dichotomy of ribosomal proteins during the synthesis of mammalian 40S ribosomal subunits. J Cell Biol 190:853–866. http://dx.doi.org/10.1083/jcb.201005117.
   PubMed Web of Science ®Google Scholar
• Perreault A, Bellemer C, Bachand F. 2008. Nuclear export competence of pre-40S subunits in fission yeast requires the ribosomal protein Rps2. Nucleic Acids Res 36:6132–6142. http://dx.doi.org/10.1093/nar/gkn625.
   PubMed Web of Science ®Google Scholar
• Moy TI, Silver PA. 2002. Requirements for the nuclear export of the small ribosomal subunit. J Cell Sci 115:2985–2995.
   PubMedGoogle Scholar
• Sivan G, Kedersha N, Elroy-Stein O. 2007. Ribosomal slowdown mediates translational arrest during cellular division. Mol Cell Biol 27:6639–6646. http://dx.doi.org/10.1128/MCB.00798-07.
   PubMed Web of Science ®Google Scholar
• Fassio CA, Schofield BJ, Seiser RM, Johnson AW, Lycan DE. 2010. Dominant mutations in the late 40S biogenesis factor Ltv1 affect cytoplasmic maturation of the small ribosomal subunit in Saccharomyces cerevisiae. Genetics 185:199–209. http://dx.doi.org/10.1534/genetics.110.115584.
   PubMed Web of Science ®Google Scholar
• Kressler D, de la Cruz J, Rojo M, Linder P. 1997. Fal1p is an essential DEAD-box protein involved in 40S-ribosomal-subunit biogenesis in Saccharomyces cerevisiae. Mol Cell Biol 17:7283–7294. http://dx.doi.org/10.1128/MCB.17.12.7283.
   PubMed Web of Science ®Google Scholar
• Ounap K, Kasper L, Kurg A, Kurg R. 2013. The human WBSCR22 protein is involved in the biogenesis of the 40S ribosomal subunits in mammalian cells. PLoS One 8:e75686. http://dx.doi.org/10.1371/journal.pone.0075686.
   PubMed Web of Science ®Google Scholar
• Lafontaine DL. 2015. Noncoding RNAs in eukaryotic ribosome biogenesis and function. Nat Struct Mol Biol 22:11–19. http://dx.doi.org/10.1038/nsmb.2939.
   PubMed Web of Science ®Google Scholar
• Tafforeau L, Zorbas C, Langhendries JL, Mullineux ST, Stamatopoulou V, Mullier R, Wacheul L, Lafontaine DL. 2013. The complexity of human ribosome biogenesis revealed by systematic nucleolar screening of pre-rRNA processing factors. Mol Cell 51:539–551. http://dx.doi.org/10.1016/j.molcel.2013.08.011.
   PubMed Web of Science ®Google Scholar
• Perez-Perez JM, Candela H, Micol JL. 2009. Understanding synergy in genetic interactions. Trends Genet 25:368–376. http://dx.doi.org/10.1016/j.tig.2009.06.004.
   PubMed Web of Science ®Google Scholar
• Fischer U, Schauble N, Schutz S, Altvater M, Chang Y, Faza MB, Panse VG. 2015. A non-canonical mechanism for Crm1-export cargo complex assembly. eLife 4:e05745. http://dx.doi.org/10.7554/eLife.05745.
   PubMed Web of Science ®Google Scholar
• Seiser RM, Sundberg AE, Wollam BJ, Zobel-Thropp P, Baldwin K, Spector MD, Lycan DE. 2006. Ltv1 is required for efficient nuclear export of the ribosomal small subunit in Saccharomyces cerevisiae. Genetics 174:679–691. http://dx.doi.org/10.1534/genetics.106.062117.
   PubMed Web of Science ®Google Scholar
• Vanrobays E, Leplus A, Osheim YN, Beyer AL, Wacheul L, Lafontaine DL. 2008. TOR regulates the subcellular distribution of DIM2, a KH domain protein required for cotranscriptional ribosome assembly and pre-40S ribosome export. RNA 14:2061–2073. http://dx.doi.org/10.1261/rna.1176708.
   PubMedGoogle Scholar
• Faza MB, Chang Y, Occhipinti L, Kemmler S, Panse VG. 2012. Role of Mex67-Mtr2 in the nuclear export of 40S pre-ribosomes. PLoS Genet 8:e1002915. http://dx.doi.org/10.1371/journal.pgen.1002915.
   PubMed Web of Science ®Google Scholar
• Oeffinger M, Dlakic M, Tollervey D. 2004. A pre-ribosome-associated HEAT-repeat protein is required for export of both ribosomal subunits. Genes Dev 18:196–209. http://dx.doi.org/10.1101/gad.285604.
   PubMed Web of Science ®Google Scholar
• Chen Q, Yan C, Yan Q, Feng L, Chen J, Qian K. 2008. The novel MGC13096 protein is correlated with proliferation. Cell Biochem Funct 26:141–145. http://dx.doi.org/10.1002/cbf.1410.
   PubMedGoogle Scholar
• Bjorklund M, Taipale M, Varjosalo M, Saharinen J, Lahdenpera J, Taipale J. 2006. Identification of pathways regulating cell size and cell-cycle progression by RNAi. Nature 439:1009–1013. http://dx.doi.org/10.1038/nature04469.
   PubMed Web of Science ®Google Scholar
• Liang L, Haug JS, Seidel CW, Gibson MC. 2014. Functional genomic analysis of the periodic transcriptome in the developing Drosophila wing. Dev Cell 29:112–127. http://dx.doi.org/10.1016/j.devcel.2014.02.018.
   PubMedGoogle Scholar