Hostname: page-component-78c5997874-v9fdk Total loading time: 0 Render date: 2024-11-10T09:13:06.145Z Has data issue: false hasContentIssue false
  • English
  • Français

TorsinA Is Functionally Associated with Spermatogenesis

Published online by Cambridge University Press:  24 September 2018

Joana B. Serrano ,
Filipa Martins ,
Cátia D. Pereira ,
Ans M. M. van Pelt ,
Odete A. B. da Cruz e Silva  and
Sandra Rebelo
Joana B. Serrano
Affiliation:
Neuroscience and Signalling Laboratory, Department of Medical Sciences, Institute of Biomedicine (iBiMED), University of Aveiro, 3810-193 Aveiro, Portugal
Filipa Martins
Affiliation:
Neuroscience and Signalling Laboratory, Department of Medical Sciences, Institute of Biomedicine (iBiMED), University of Aveiro, 3810-193 Aveiro, Portugal
Cátia D. Pereira
Affiliation:
Neuroscience and Signalling Laboratory, Department of Medical Sciences, Institute of Biomedicine (iBiMED), University of Aveiro, 3810-193 Aveiro, Portugal
Ans M. M. van Pelt
Affiliation:
Center for Reproductive Medicine, Research Institute Reproduction and Development, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Odete A. B. da Cruz e Silva
Affiliation:
Neuroscience and Signalling Laboratory, Department of Medical Sciences, Institute of Biomedicine (iBiMED), University of Aveiro, 3810-193 Aveiro, Portugal The Discovery CTR, University of Aveiro Campus, 3810-193 Aveiro, Portugal
Sandra Rebelo*
Affiliation:
Neuroscience and Signalling Laboratory, Department of Medical Sciences, Institute of Biomedicine (iBiMED), University of Aveiro, 3810-193 Aveiro, Portugal
*
Author for correspondence: Sandra Rebelo, E-mail: srebelo@ua.pt
Get access

Abstract

TorsinA is a member of the AAA+ superfamily of adenosine triphosphatases. These AAA+ proteins have numerous biological functions, including vesicle fusion, cytoskeleton dynamics, intracellular trafficking, protein folding, and degradation as well as organelle biogenesis. Of particular interest is torsinA, which is mainly located in the endoplasmic reticulum (ER) and nuclear envelope (NE). Interestingly, mutations in the TOR1A gene (the gene encoding torsinA) are associated with DYT1 dystonia and with the preferential localization of mutated torsinA at the NE, where it is associated with lamina-associated polypeptide 1. A bioinformatics study of the torsinA interactome revealed reproductive processes to be highly relevant, as proteins in this class were found to interact with the former. Interestingly, the torsin protein family had never been previously described to be associated with the mammalian spermatogenic process. Histological staining of torsinA in human testis tissue revealed a granular cytoplasmic localization in mid- and late spermatocytes. We further sought to understand this newly discovered expression of torsinA in the meiotic phase of human spermatogenesis by studying its specific subcellular distribution. TorsinA is not present in the ER as commonly described. The proposal that torsinA might relocate to the pro-acrosomal vesicles in the Golgi apparatus is discussed.

Keywords

endoplasmic reticulumgolgi apparatusnuclear envelopetorsinAspermatogenesis
Type
Life Sciences
Information
Microscopy and Microanalysis , Volume 25 , Issue 1 , February 2019 , pp. 221 - 228
Copyright
Copyright © Microscopy Society of America 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

a

Both authors contributed equally to this work.

References

Alsheimer, M, Fecher, E Benavente, R (1998) Nuclear envelope remodelling during rat spermiogenesis: Distribution and expression pattern of LAP2/thymopoietins. J Cell Sci 111(Pt 15), 2227–2234.Google Scholar
Alsheimer, M, von Glasenapp, E, Hock, R Benavente, R (1999) Architecture of the nuclear periphery of rat pachytene spermatocytes: Distribution of nuclear envelope proteins in relation to synaptonemal complex attachment sites. Mol Biol Cell 10(4), 1235–1245.Google Scholar
Basham, SE Rose, LS (1999) Mutations in ooc-5 and ooc-3 disrupt oocyte formation and the reestablishment of asymmetric PAR protein localization in two-cell Caenorhabditis elegans embryos. Dev Biol 215(2), 253–263.Google Scholar
Basham, SE Rose, LS (2001) The Caenorhabditis elegans polarity gene ooc-5 encodes a Torsin-related protein of the AAA ATPase superfamily. Development 128(22), 4645–4656.Google Scholar
Bellve, AR, Cavicchia, JC, Millette, CF, O’Brien, DA, Bhatnagar, YM Dym, M (1977) Spermatogenic cells of the prepuberal mouse. Isolation and morphological characterization. J Cell Biol 74(1), 68–85.Google Scholar
Brown, RS, Zhao, C, Chase, AR, Wang, J Schlieker, C (2014) The mechanism of Torsin ATPase activation. Proc Natl Acad Sci U S A 111(45), E4822–E4831.Google Scholar
Burdette, AJ, Churchill, PF, Caldwell, GA Caldwell, KA (2010) The early-onset torsion dystonia-associated protein, torsinA, displays molecular chaperone activity in vitro. Cell Stress Chaperones 15(5), 605–617.Google Scholar
Calvi, A, Wong, AS, Wright, G, Wong, ES, Loo, TH, Stewart, CL Burke, B (2015) SUN4 is essential for nuclear remodeling during mammalian spermiogenesis. Dev Biol 407(2), 321–330.Google Scholar
Chen, P, Burdette, AJ, Porter, JC, Ricketts, JC, Fox, SA, Nery, FC, Hewett, JW, Berkowitz, LA, Breakefield, XO, Caldwell, KA Caldwell, GA (2010) The early-onset torsion dystonia-associated protein, torsinA, is a homeostatic regulator of endoplasmic reticulum stress response. Hum Mol Genet 19(18), 3502–3515.Google Scholar
Ding, X, Xu, R, Yu, J, Xu, T, Zhuang, Y Han, M (2007) SUN1 is required for telomere attachment to nuclear envelope and gametogenesis in mice. Dev Cell 12(6), 863–872.Google Scholar
Frohnert, C, Schweizer, S Hoyer-Fender, S (2011) SPAG4L/SPAG4L-2 are testis-specific SUN domain proteins restricted to the apical nuclear envelope of round spermatids facing the acrosome. Mol Hum Reprod 17(4), 207–218.Google Scholar
Giles, LM, Li, L Chin, LS (2009) Printor, a novel torsinA-interacting protein implicated in dystonia pathogenesis. J Biol Chem 284(32), 21765–21775.Google Scholar
Gob, E, Schmitt, J, Benavente, R Alsheimer, M (2010) Mammalian sperm head formation involves different polarization of two novel LINC complexes. PLoS One 5(8), e12072.Google Scholar
Gonzalez-Alegre, P Paulson, HL (2004) Aberrant cellular behavior of mutant torsinA implicates nuclear envelope dysfunction in DYT1 dystonia. J Neurosci 24(11), 2593–2601.Google Scholar
Goodchild, RE Dauer, WT (2004) Mislocalization to the nuclear envelope: An effect of the dystonia-causing torsinA mutation. Proc Natl Acad Sci U S A 101(3), 847–852.Google Scholar
Goodchild, RE Dauer, WT (2005) The AAA+ protein torsinA interacts with a conserved domain present in LAP1 and a novel ER protein. J Cell Biol 168(6), 855–862.Google Scholar
Hermo, L, Pelletier, RM, Cyr, DG Smith, CE (2010) Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 1: Background to spermatogenesis, spermatogonia, and spermatocytes. Microsc Res Tech 73(4), 241–278.Google Scholar
Hewett, J, Ziefer, P, Bergeron, D, Naismith, T, Boston, H, Slater, D, Wilbur, J, Schuback, D, Kamm, C, Smith, N, Camp, S, Ozelius, LJ, Ramesh, V, Hanson, PI Breakefield, XO (2003) TorsinA in PC12 cells: Localization in the endoplasmic reticulum and response to stress. J Neurosci Res 72(2), 158–168.Google Scholar
Hewett, JW, Nery, FC, Niland, B, Ge, P, Tan, P, Hadwiger, P, Tannous, BA, Sah, DW Breakefield, XO (2008) siRNA knock-down of mutant torsinA restores processing through secretory pathway in DYT1 dystonia cells. Hum Mol Genet 17(10), 1436–1445.Google Scholar
Hewett, JW, Tannous, B, Niland, BP, Nery, FC, Zeng, J, Li, Y Breakefield, XO (2007) Mutant torsinA interferes with protein processing through the secretory pathway in DYT1 dystonia cells. Proc Natl Acad Sci U S A 104(17), 7271–7276.Google Scholar
Horn, HF, Kim, DI, Wright, GD, Wong, ES, Stewart, CL, Burke, B Roux, KJ (2013) A mammalian KASH domain protein coupling meiotic chromosomes to the cytoskeleton. J Cell Biol 202(7), 1023–1039.Google Scholar
Huang da, W, Sherman, BT Lempicki, RA (2009 a) Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37(1), 1–13.Google Scholar
Huang da, W, Sherman, BT Lempicki, RA (2009 b) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4(1), 44–57.Google Scholar
Jokhi, V, Ashley, J, Nunnari, J, Noma, A, Ito, N, Wakabayashi-Ito, N, Moore, MJ Budnik, V (2013) Torsin mediates primary envelopment of large ribonucleoprotein granules at the nuclear envelope. Cell Rep 3(4), 988–995.Google Scholar
Jungwirth, MT, Kumar, D, Jeong, DY Goodchild, RE (2011) The nuclear envelope localization of DYT1 dystonia torsinA-DeltaE requires the SUN1 LINC complex component. BMC Cell Biol 12, 24.Google Scholar
Kustedjo, K, Bracey, MH Cravatt, BF (2000) Torsin A and its torsion dystonia-associated mutant forms are lumenal glycoproteins that exhibit distinct subcellular localizations. J Biol Chem 275(36), 27933–27939.Google Scholar
Link, J, Leubner, M, Schmitt, J, Gob, E, Benavente, R, Jeang, KT, Xu, R Alsheimer, M (2014) Analysis of meiosis in SUN1 deficient mice reveals a distinct role of SUN2 in mammalian meiotic LINC complex formation and function. PLoS Genet 10(2), e1004099.Google Scholar
Moreno, RD, Ramalho-Santos, J, Sutovsky, P, Chan, EK Schatten, G (2000) Vesicular traffic and golgi apparatus dynamics during mammalian spermatogenesis: Implications for acrosome architecture. Biol Reprod 63(1), 89–98.Google Scholar
Mylonis, I, Drosou, V, Brancorsini, S, Nikolakaki, E, Sassone-Corsi, P Giannakouros, T (2004) Temporal association of protamine 1 with the inner nuclear membrane protein lamin B receptor during spermiogenesis. J Biol Chem 279(12), 11626–11631.Google Scholar
Naismith, TV, Heuser, JE, Breakefield, XO Hanson, PI (2004) TorsinA in the nuclear envelope. Proc Natl Acad Sci U S A 101(20), 7612–7617.Google Scholar
Nery, FC, Armata, IA, Farley, JE, Cho, JA, Yaqub, U, Chen, P, da Hora, CC, Wang, Q, Tagaya, M, Klein, C, Tannous, B, Caldwell, KA, Caldwell, GA, Lencer, WI, Ye, Y Breakefield, XO (2011) TorsinA participates in endoplasmic reticulum-associated degradation. Nat Commun 2, 393.Google Scholar
Nery, FC, Zeng, J, Niland, BP, Hewett, J, Farley, J, Irimia, D, Li, Y, Wiche, G, Sonnenberg, A Breakefield, XO (2008) TorsinA binds the KASH domain of nesprins and participates in linkage between nuclear envelope and cytoskeleton. J Cell Sci 121(Pt 20), 3476–3486.Google Scholar
Pierre, V, Martinez, G, Coutton, C, Delaroche, J, Yassine, S, Novella, C, Pernet-Gallay, K, Hennebicq, S, Ray, PF Arnoult, C (2012) Absence of Dpy19l2, a new inner nuclear membrane protein, causes globozoospermia in mice by preventing the anchoring of the acrosome to the nucleus. Development 139(16), 2955–2965.Google Scholar
Rittiner, JE, Caffall, ZF, Hernandez-Martinez, R, Sanderson, SM, Pearson, JL, Tsukayama, KK, Liu, AY, Xiao, C, Tracy, S, Shipman, MK, Hickey, P, Johnson, J, Scott, B, Stacy, M, Saunders-Pullman, R, Bressman, S, Simonyan, K, Sharma, N, Ozelius, LJ, Cirulli, ET Calakos, N (2016) Functional genomic analyses of Mendelian and sporadic disease identify impaired eIF2alpha signaling as a generalizable mechanism for dystonia. Neuron 92(6), 1238–1251.Google Scholar
Schindelin, J, Arganda-Carreras, I, Frise, E, Kaynig, V, Longair, M, Pietzsch, T, Preibisch, S, Rueden, C, Saalfeld, S, Schmid, B, Tinevez, JY, White, DJ, Hartenstein, V, Eliceiri, K, Tomancak, P Cardona, A (2012) Fiji: an open-source platform for biological-image analysis. Nat Methods 9(7), 676–682.Google Scholar
Schmitt, J, Benavente, R, Hodzic, D, Hoog, C, Stewart, CL Alsheimer, M (2007) Transmembrane protein Sun2 is involved in tethering mammalian meiotic telomeres to the nuclear envelope. Proc Natl Acad Sci U S A 104(18), 7426–7431.Google Scholar
Schutz, W, Benavente, R Alsheimer, M (2005) Dynamic properties of germ line-specific lamin B3: the role of the shortened rod domain. Eur J Cell Biol 84(7), 649–662.Google Scholar
Serrano, JB, Martins, F, Sousa, JC, Pereira, CD, van Pelt, AM, Rebelo, S da Cruz e, Silva OA (2017) Descriptive analysis of LAP1 distribution and that of associated proteins throughout spermatogenesis. Membranes (Basel) 7(2), E22.Google Scholar
Shannon, P, Markiel, A, Ozier, O, Baliga, NS, Wang, JT, Ramage, D, Amin, N, Schwikowski, B Ideker, T (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13(11), 2498–2504.Google Scholar
Shen, J, Chen, W, Shao, B, Qi, Y, Xia, Z, Wang, F, Wang, L, Guo, X, Huang, X Sha, J (2014) Lamin A/C proteins in the spermatid acroplaxome are essential in mouse spermiogenesis. Reproduction 148(5), 479–487.Google Scholar
Sosa, BA, Demircioglu, FE, Chen, JZ, Ingram, J, Ploegh, HL Schwartz, TU (2014) How lamina-associated polypeptide 1 (LAP1) activates Torsin. Elife 3, e03239.Google Scholar
Tanabe, LM, Liang, CC Dauer, WT (2016) Neuronal nuclear membrane budding occurs during a developmental window modulated by Torsin Paralogs. Cell Rep 16(12), 3322–3333.Google Scholar
Uhlen, M, Fagerberg, L, Hallstrom, BM, Lindskog, C, Oksvold, P, Mardinoglu, A, Sivertsson, A, Kampf, C, Sjostedt, E, Asplund, A, Olsson, I, Edlund, K, Lundberg, E, Navani, S, Szigyarto, CA, Odeberg, J, Djureinovic, D, Takanen, JO, Hober, S, Alm, T, Edqvist, PH, Berling, H, Tegel, H, Mulder, J, Rockberg, J, Nilsson, P, Schwenk, JM, Hamsten, M, von Feilitzen, K, Forsberg, M, Persson, L, Johansson, F, Zwahlen, M, von Heijne, G, Nielsen, J Ponten, F (2015) Proteomics. Tissue-based map of the human proteome. Science 347(6220), 1260419.Google Scholar
VanGompel, MJ, Nguyen, KC, Hall, DH, Dauer, WT Rose, LS (2015) A novel function for the Caenorhabditis elegans torsin OOC-5 in nucleoporin localization and nuclear import. Mol Biol Cell 26(9), 1752–1763.Google Scholar
Zhao, C, Brown, RS, Chase, AR, Eisele, MR Schlieker, C (2013) Regulation of Torsin ATPases by LAP1 and LULL1. Proc Natl Acad Sci U S A 110(17), E1545-E1554.Google Scholar
Supplementary material: File

Serrano et al. supplementary material

Table S1

Download Serrano et al. supplementary material(File)
File 14.9 KB
Supplementary material: File

Serrano et al. supplementary material

Table S2

Download Serrano et al. supplementary material(File)
File 25.8 KB
Supplementary material: File

Serrano et al. supplementary material

Table S3

Download Serrano et al. supplementary material(File)
File 12.6 KB