Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Torsin 1A Interacting Protein 1

  • Joana B. Serrano
  • Filipa Martins
  • Ana M. Marafona
  • Odete A. B. da Cruz e Silva
  • Sandra RebeloEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101846


Historical Background

Lamina associated polypeptide 1 (LAP1) was identified in 1988 as an integral inner nuclear membrane (INM) protein associated with lamins. LAP1 family members were identified using a monoclonal antibody against rat liver nuclear envelope (NE) extracts (Senior and Gerace 1988). This antibody recognized three polypeptides with apparent molecular weights of 75 KDa, 68 KDa, and 55 KDa in rat liver NEs that were subsequently termed LAP1A, LAP1B, and LAP1C, respectively. The evidence that LAP1 was connected to nuclear lamina was achieved by biochemical extraction experiments, and subsequent in vitro experiments demonstrated that LAP1A and LAP1B bind directly to lamins A, C, and B1 and most likely indirectly to chromosomes (Foisner and Gerace 1993). Further co-immunoprecipitation studies demonstrated that LAP1A/LAP1C co-immunoprecipitated...

This is a preview of subscription content, log in to check access.


  1. Arnoult N, Karlseder J. Complex interactions between the DNA-damage response and mammalian telomeres. Nat Struct Mol Biol. 2015;22:859–66.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Bione S, Maestrini E, Rivella S, Mancini M, Regis S, Romeo G, Toniolo D. Identification of a novel X-linked gene responsible for Emery-Dreifuss muscular dystrophy. Nat Genet. 1994;8:323–7.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Brown RS, Zhao C, Chase AR, Wang J, Schlieker C. The mechanism of Torsin ATPase activation. Proc Natl Acad Sci USA. 2014;111:E4822–31.PubMedPubMedCentralCrossRefGoogle Scholar
  4. de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 2005;19:2100–10.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Dorboz I, Coutelier M, Bertrand AT, Caberg JH, Elmaleh-Berges M, Laine J, Stevanin G, Bonne G, Boespflug-Tanguy O, Servais L. Severe dystonia, cerebellar atrophy, and cardiomyopathy likely caused by a missense mutation in TOR1AIP1. Orphanet J Rare Dis. 2014;9:174.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Foisner R, Gerace L. Integral membrane proteins of the nuclear envelope interact with lamins and chromosomes, and binding is modulated by mitotic phosphorylation. Cell. 1993;73:1267–79.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Ghaoui R, Benavides T, Lek M, Waddell LB, Kaur S, North KN, MacArthur DG, Clarke NF, Cooper ST. TOR1AIP1 as a cause of cardiac failure and recessive limb-girdle muscular dystrophy. Neuromuscul Disord. 2016;26:500–3.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Goodchild RE, Dauer WT. Mislocalization to the nuclear envelope: an effect of the dystonia-causing torsinA mutation. Proc Natl Acad Sci USA. 2004;101:847–52.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Goodchild RE, Dauer WT. The AAA+ protein torsinA interacts with a conserved domain present in LAP1 and a novel ER protein. J Cell Biol. 2005;168:855–62.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Hutchins JR, Toyoda Y, Hegemann B, Poser I, Heriche JK, Sykora MM, Augsburg M, Hudecz O, Buschhorn BA, Bulkescher J, Conrad C, Comartin D, Schleiffer A, Sarov M, Pozniakovsky A, Slabicki MM, Schloissnig S, Steinmacher I, Leuschner M, Ssykor A, Lawo S, Pelletier L, Stark H, Nasmyth K, Ellenberg J, Durbin R, Buchholz F, Mechtler K, Hyman AA, Peters JM. Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science. 2010;328:593–9.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Kayman-Kurekci G, Talim B, Korkusuz P, Sayar N, Sarioglu T, Oncel I, Sharafi P, Gundesli H, Balci-Hayta B, Purali N, Serdaroglu-Oflazer P, Topaloglu H, Dincer P. Mutation in TOR1AIP1 encoding LAP1B in a form of muscular dystrophy: a novel gene related to nuclear envelopathies. Neuromuscul Disord. 2014;24:624–33.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Kim CE, Perez A, Perkins G, Ellisman MH, Dauer WT. A molecular mechanism underlying the neural-specific defect in torsinA mutant mice. Proc Natl Acad Sci USA. 2010;107:9861–6.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Kondo Y, Kondoh J, Hayashi D, Ban T, Takagi M, Kamei Y, Tsuji L, Kim J, Yoneda Y. Molecular cloning of one isotype of human lamina-associated polypeptide 1s and a topological analysis using its deletion mutants. Biochem Biophys Res Commun. 2002;294:770–8.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Laudermilch E, Schlieker C. Torsin ATPases: structural insights and functional perspectives. Curr Opin Cell Biol. 2016;40:1–7.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Maison C, Pyrpasopoulou A, Theodoropoulos PA, Georgatos SD. The inner nuclear membrane protein LAP1 forms a native complex with B-type lamins and partitions with spindle-associated mitotic vesicles. EMBO J. 1997;16:4839–50.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Manilal S, Recan D, Sewry CA, Hoeltzenbein M, Llense S, Leturcq F, Deburgrave N, Barbot J, Man N, Muntoni F, Wehnert M, Kaplan J, Morris GE. Mutations in Emery-Dreifuss muscular dystrophy and their effects on emerin protein expression. Hum Mol Genet. 1998;7:855–64.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Martin L, Crimaudo C, Gerace L. cDNA cloning and characterization of lamina-associated polypeptide 1C (LAP1C), an integral protein of the inner nuclear membrane. J Biol Chem. 1995;270:8822–8.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Neumann B, Walter T, Heriche JK, Bulkescher J, Erfle H, Conrad C, Rogers P, Poser I, Held M, Liebel U, Cetin C, Sieckmann F, Pau G, Kabbe R, Wunsche A, Satagopam V, Schmitz MH, Chapuis C, Gerlich DW, Schneider R, Eils R, Huber W, Peters JM, Hyman AA, Durbin R, Pepperkok R, Ellenberg J. Phenotypic profiling of the human genome by time-lapse microscopy reveals cell division genes. Nature. 2010;464:721–7.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Ozelius LJ, Hewett JW, Page CE, Bressman SB, Kramer PL, Shalish C, de Leon D, Brin MF, Raymond D, Corey DP, Fahn S, Risch NJ, Buckler AJ, Gusella JF, Breakefield XO. The early-onset torsion dystonia gene (DYT1) encodes an ATP-binding protein. Nat Genet. 1997;17:40–8.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Rebelo S, da Cruz ESEF, da Cruz ESOA. Genetic mutations strengthen functional association of LAP1 with DYT1 dystonia and muscular dystrophy. Mutat Res Rev Mutat Res. 2015a;766:42–7.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Rebelo S, Santos M, Martins F, da Cruz ESEF, da Cruz ESOA. Protein phosphatase 1 is a key player in nuclear events. Cell Signal. 2015b;27:2589–98.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Santos M, Rebelo S, Van Kleeff PJ, Kim CE, Dauer WT, Fardilha M, da Cruz ESOA, da Cruz ESEF. The nuclear envelope protein, LAP1B, is a novel protein phosphatase 1 substrate. Plos One. 2013;8:e76788.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Santos M, Domingues SC, Costa P, Muller T, Galozzi S, Marcus K, da Cruz ESEF, da Cruz ESOA, Rebelo S. Identification of a novel human LAP1 Isoform that is regulated by protein phosphorylation. Plos One. 2014;9:e113732.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Santos M, Costa P, Martins F, da Cruz e Silva EF, da Cruz e Silva OA, Rebelo S. LAP1 is a crucial protein for the maintenance of the nuclear envelope structure and cell cycle progression. Mol Cell Biochem. 2015;399:143–153.Google Scholar
  25. Schirmer EC, Foisner R. Proteins that associate with lamins: many faces, many functions. Exp Cell Res. 2007;313:2167–79.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Senior A, Gerace L. Integral membrane proteins specific to the inner nuclear membrane and associated with the nuclear lamina. J Cell Biol. 1988;107:2029–36.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Serrano JB, da Cruz ESOA, Rebelo S. Lamina associated polypeptide 1 (LAP1) interactome and its functional features. Membranes (Basel). 2016a;6. doi:10.3390/membranes6010008.CrossRefPubMedCentralGoogle Scholar
  28. Serrano JB, Martins F, Sousa JC, van Pelt AMM, Rebelo S, da Cruz e Silva OAB. The distribution of LAP1 and associated proteins throughout spermatogenesis. Reprod Fertil Dev (submitted). 2016b.Google Scholar
  29. Shin JY, Mendez-Lopez I, Wang Y, Hays AP, Tanji K, Lefkowitch JH, Schulze PC, Worman HJ, Dauer WT. Lamina-associated polypeptide-1 interacts with the muscular dystrophy protein emerin and is essential for skeletal muscle maintenance. Dev Cell. 2013;26:591–603.PubMedPubMedCentralCrossRefGoogle Scholar
  30. Sosa BA, Demircioglu FE, Chen JZ, Ingram J, Ploegh HL, Schwartz TU. How lamina-associated polypeptide 1 (LAP1) activates Torsin. Elife. 2014;3:e03239.PubMedPubMedCentralCrossRefGoogle Scholar
  31. Tadokoro K, Yamazaki-Inoue M, Tachibana M, Fujishiro M, Nagao K, Toyoda M, Ozaki M, Ono M, Miki N, Miyashita T, Yamada M. Frequent occurrence of protein isoforms with or without a single amino acid residue by subtle alternative splicing: the case of Gln in DRPLA affects subcellular localization of the products. J Hum Genet. 2005;50:382–94.PubMedPubMedCentralCrossRefGoogle Scholar
  32. Zhao C, Brown RS, Chase AR, Eisele MR, Schlieker C. Regulation of Torsin ATPases by LAP1 and LULL1. Proc Natl Acad Sci USA. 2013;110:E1545–54.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Joana B. Serrano
    • 1
  • Filipa Martins
    • 1
  • Ana M. Marafona
    • 1
  • Odete A. B. da Cruz e Silva
    • 1
  • Sandra Rebelo
    • 1
    Email author
  1. 1.Neuroscience and Signaling Laboratory, Department of Medical Sciences, Institute of Biomedicine-iBiMEDUniversity of AveiroAveiroPortugal