BICD2

Summary

Gene Symbol: BICD2
Description: BICD cargo adaptor 2
Alias: SMALED2, bA526D8.1, protein bicaudal D homolog 2, bic-D 2, bicaudal D homolog 2, coiled-coil protein BICD2, cytoskeleton-like bicaudal D protein homolog 2, homolog of Drosophila bicaudal D
Species: human
Products:     BICD2

Top Publications

  1. Hoogenraad C, Akhmanova A, Howell S, Dortland B, De Zeeuw C, Willemsen R, et al. Mammalian Golgi-associated Bicaudal-D2 functions in the dynein-dynactin pathway by interacting with these complexes. EMBO J. 2001;20:4041-54 pubmed
    ..We show here that a mammalian homologue of Bicaudal-D, BICD2, binds to the dynamitin subunit of dynactin...
  2. Short B, Preisinger C, Schaletzky J, Kopajtich R, Barr F. The Rab6 GTPase regulates recruitment of the dynactin complex to Golgi membranes. Curr Biol. 2002;12:1792-5 pubmed
    ..Other Golgi Rabs do not bind to dynactin and are unable to support its recruitment to membranes. Rab6 therefore functions as a specificity or tethering factor controlling the recruitment of dynactin to membranes. ..
  3. Matanis T, Akhmanova A, Wulf P, del Nery E, Weide T, Stepanova T, et al. Bicaudal-D regulates COPI-independent Golgi-ER transport by recruiting the dynein-dynactin motor complex. Nat Cell Biol. 2002;4:986-92 pubmed
    ..BICD1 and BICD2 colocalize with Rab6a on the trans-Golgi network (TGN) and on cytoplasmic vesicles, and associate with Golgi ..
  4. Hoogenraad C, Wulf P, Schiefermeier N, Stepanova T, Galjart N, Small J, et al. Bicaudal D induces selective dynein-mediated microtubule minus end-directed transport. EMBO J. 2003;22:6004-15 pubmed
    ..Here we report that the N-terminal portion of human Bicaudal D2 (BICD2) is capable of inducing microtubule minus end-directed movement independently of the molecular context...
  5. Splinter D, Tanenbaum M, Lindqvist A, Jaarsma D, Flotho A, Yu K, et al. Bicaudal D2, dynein, and kinesin-1 associate with nuclear pore complexes and regulate centrosome and nuclear positioning during mitotic entry. PLoS Biol. 2010;8:e1000350 pubmed publisher
    b>BICD2 is one of the two mammalian homologues of the Drosophila Bicaudal D, an evolutionarily conserved adaptor between microtubule motors and their cargo that was previously shown to link vesicles and mRNP complexes to the dynein motor...
  6. Gonçalves J, Dantas T, Vallee R. Distinct roles for dynein light intermediate chains in neurogenesis, migration, and terminal somal translocation. J Cell Biol. 2019;218:808-819 pubmed publisher
    ..We find that LIC1, through BicD2, is required for apical nuclear migration in neural progenitors...
  7. Martínez Carrera L, Gabriel E, Donohoe C, Holker I, Mariappan A, Storbeck M, et al. Novel insights into SMALED2: BICD2 mutations increase microtubule stability and cause defects in axonal and NMJ development. Hum Mol Genet. 2018;27:1772-1784 pubmed publisher
    ..Heterozygous mutations in BICD2 cause autosomal dominant lower extremity-predominant spinal muscular atrophy-2 (SMALED2)...
  8. Olenick M, Holzbaur E. Dynein activators and adaptors at a glance. J Cell Sci. 2019;132: pubmed publisher
    ..Activating adaptors such as BICD2 and Hook1 enhance the stability of the complex that dynein forms with its required activator dynactin, leading to ..
  9. Lee H, Jung Y, Oh J, Choi G, Chae C, Kim J, et al. BICD1 mediates HIF1α nuclear translocation in mesenchymal stem cells during hypoxia adaptation. Cell Death Differ. 2018;: pubmed publisher
    ..In our results, silencing of BICD1 but not BICD2 abolished HIF1α nuclear translocation and its activity...

More Information

Publications57

  1. Xia B, Li Y, Zhou J, Tian B, Feng L. Identification of potential pathogenic genes associated with osteoporosis. Bone Joint Res. 2017;6:640-648 pubmed publisher
    ..Genes such as VPS35, FCGR2A, TBCA, HIRA, TYROBP, JUND, PHF20, NFKB2, RPL35A and BICD2 may be considered to be potential pathogenic genes of osteoporosis and may be useful for further study of the ..
  2. Urnavicius L, Lau C, Elshenawy M, Morales Ríos E, Motz C, Yildiz A, et al. Cryo-EM shows how dynactin recruits two dyneins for faster movement. Nature. 2018;554:202-206 pubmed publisher
    ..its cofactor dynactin form a highly processive microtubule motor in the presence of an activating adaptor, such as BICD2. Different adaptors link dynein and dynactin to distinct cargoes...
  3. Peeters K, Bervoets S, Chamova T, Litvinenko I, De Vriendt E, Bichev S, et al. Novel mutations in the DYNC1H1 tail domain refine the genetic and clinical spectrum of dyneinopathies. Hum Mutat. 2015;36:287-91 pubmed publisher
    ..The mutations in DYNC1H1 increase the interaction with its adaptor BICD2. This relates to previous studies on BICD2 mutations causing a highly similar phenotype...
  4. Carnes S, Zhou J, Aiken C. HIV-1 Engages a Dynein-Dynactin-BICD2 Complex for Infection and Transport to the Nucleus. J Virol. 2018;92: pubmed publisher
    ..interfering RNA depletion of the dynein heavy chain, components of the dynactin complex, and the dynein adaptor BICD2 reduced cell permissiveness to HIV-1 infection...
  5. Koboldt D, Kastury R, Waldrop M, Kelly B, Mihalic Mosher T, McLaughlin H, et al. Inframe de novo mutation in BICD2 in two patients with muscular atrophy and arthrogryposis. Cold Spring Harb Mol Case Stud. 2018;: pubmed publisher
    ..Missense mutations in BICD2 cause autosomal dominant spinal muscular atrophy, lower-extremity predominant 2 (SMALED2), a disease characterized by muscle weakness and arthrogryposis of early onset and slow progression. The p...
  6. Bucukovski J, Carter J, Striemer C, Müllner S, Schulte Pelkum J, Schulz Knappe P, et al. Label-free microarray-based detection of autoantibodies in human serum. J Immunol Methods. 2018;459:44-49 pubmed publisher
    ..In this work, we demonstrate that AIR is able to detect antibodies to Ro60, La/SSB, Scl-70, BicD2, and Ro52 in single-donor human serum samples with multiplex results comparable to singleplex ELISA or Luminex ..
  7. Chang Y, Chang C, Huang H, Lin C, Yeh K, Chang J. Detection of Molecular Alterations in Taiwanese Patients with Medullary Thyroid Cancer Using Whole-Exome Sequencing. Endocr Pathol. 2018;29:324-331 pubmed publisher
    ..We detected new somatic mutations in the BICD2, DLG1, FSD2, IL17RD, KLHL25, PAPPA2, PRDM2, PSEN1, SCRN1, and TTC1 genes...
  8. Schlager M, Hoang H, Urnavicius L, Bullock S, Carter A. In vitro reconstitution of a highly processive recombinant human dynein complex. EMBO J. 2014;33:1855-68 pubmed publisher
    ..However, addition of dynactin together with the N-terminal region of the cargo adaptor BICD2 (BICD2N) gives rise to unidirectional dynein movement over remarkably long distances...
  9. Asante D, Stevenson N, Stephens D. Subunit composition of the human cytoplasmic dynein-2 complex. J Cell Sci. 2014;127:4774-87 pubmed publisher
    ..By contrast, the common dynein-1 regulators dynactin, LIS1 (also known as PAFAH1B1) and BICD2 are not found in association with dynein-2...
  10. McKenney R, Huynh W, Vale R, Sirajuddin M. Tyrosination of α-tubulin controls the initiation of processive dynein-dynactin motility. EMBO J. 2016;35:1175-85 pubmed publisher
    ..Here, we examined the processive motility of mammalian dynein complexed with dynactin and BicD2 (DDB) on tyrosinated versus detyrosinated microtubules...
  11. Yoshioka M, Morisada N, Toyoshima D, Yoshimura H, Nishio H, Iijima K, et al. Novel BICD2 mutation in a Japanese family with autosomal dominant lower extremity-predominant spinal muscular atrophy-2. Brain Dev. 2018;40:343-347 pubmed publisher
    ..Genetic studies in this family revealed a novel BICD2 mutation causing autosomal dominant lower extremity-predominant SMA type 2...
  12. Olenick M, Tokito M, Boczkowska M, Dominguez R, Holzbaur E. Hook Adaptors Induce Unidirectional Processive Motility by Enhancing the Dynein-Dynactin Interaction. J Biol Chem. 2016;291:18239-51 pubmed publisher
    ..inducing longer run lengths and higher velocities than the previously characterized dynein activator bicaudal D2 (BICD2)...
  13. Goldberg M. Nuclear pore complex tethers to the cytoskeleton. Semin Cell Dev Biol. 2017;68:52-58 pubmed publisher
    ..linked, most importantly, to the cytoplasmic filament protein of the nuclear pore complex, Nup358, by the adaptor BicD2. The evidence for such linkages and possible roles in nuclear migration, cell cycle control, nuclear transport and ..
  14. Carter A, Diamant A, Urnavicius L. How dynein and dynactin transport cargos: a structural perspective. Curr Opin Struct Biol. 2016;37:62-70 pubmed publisher
    ..revealed the structure of dynactin and how it binds dynein in the presence of a cargo adaptor protein Bicaudal-D2 (BICD2). Future questions will include how dynein-1 transports so many different cargos and how the 2...
  15. Li H, Sun L, Li H, Lv X, Semukunzi H, Li R, et al. DT-13 synergistically enhanced vinorelbine-mediated mitotic arrest through inhibition of FOXM1-BICD2 axis in non-small-cell lung cancer cells. Cell Death Dis. 2017;8:e2810 pubmed publisher
    ..that nuclear expression of transcription factors forkhead box M1 (FOXM1) and levels of motor adaptor bicaudal D2 (BICD2) were dramatically reduced by combination treatment...
  16. Juntas Morales R, Pageot N, Taieb G, Camu W. Adult-onset spinal muscular atrophy: An update. Rev Neurol (Paris). 2017;173:308-319 pubmed publisher
    ..in which the causative gene has been identified (SMN1-related SMA, Kennedy disease, CHCHD10, TRPV4, DYNC1H1 and BICD2). Sporadic lower motor neuron disease, also known as progressive muscular atrophy (PMA), is also discussed...
  17. Lee I, Olenick M, Boczkowska M, Franzini Armstrong C, Holzbaur E, Dominguez R. A conserved interaction of the dynein light intermediate chain with dynein-dynactin effectors necessary for processivity. Nat Commun. 2018;9:986 pubmed publisher
    ..studies map these interactions to a conserved helix within LIC1 and to N-terminal fragments of Hook1, Hook3, BICD2, and Spindly...
  18. Belyy V, Schlager M, Foster H, Reimer A, Carter A, Yildiz A. The mammalian dynein-dynactin complex is a strong opponent to kinesin in a tug-of-war competition. Nat Cell Biol. 2016;18:1018-24 pubmed publisher
    ..Mammalian dynein's association with dynactin and Bicaudal-D2 (BICD2) activates its processive motility, but it was unknown how this affects dynein's force output...
  19. Ravenscroft G, Di Donato N, Hahn G, Davis M, Craven P, Poke G, et al. Recurrent de novo BICD2 mutation associated with arthrogryposis multiplex congenita and bilateral perisylvian polymicrogyria. Neuromuscul Disord. 2016;26:744-748 pubmed publisher
    Autosomal dominantly inherited mutations of BICD2 are associated with congenital-onset spinal muscular atrophy characterised by lower limb predominance...
  20. Beecroft S, McLean C, Delatycki M, Koshy K, Yiu E, Haliloglu G, et al. Expanding the phenotypic spectrum associated with mutations of DYNC1H1. Neuromuscul Disord. 2017;27:607-615 pubmed publisher
    ..We also highlight features that increase the phenotypic overlap with BICD2, which causes SMALED2. Serial muscle biopsies were available for several patients, spanning from infancy and early childhood to middle ..
  21. Guo Y, Zheng Y. Lamins position the nuclear pores and centrosomes by modulating dynein. Mol Biol Cell. 2015;26:3379-89 pubmed publisher
    ..NPC distribution in the absence of lamins is caused by dynein forces acting on NPCs via the dynein adaptor BICD2. We further show that asymmetric NPC distribution upon lamin depletion disrupts the distribution of BICD2 and p150 ..
  22. Oe S, Miki H, Nishimura W, Noda Y. Mechanism of the Dendritic Translation and Localization of Brain-derived Neurotrophic Factor. Cell Struct Funct. 2016;41:23-31 pubmed publisher
    ..Further, locally synthesized BDNF vesicles co-localized with Bicaudal-D2 (BicD2), a member of dynein motor complex proteins...
  23. Hoang H, Schlager M, Carter A, Bullock S. DYNC1H1 mutations associated with neurological diseases compromise processivity of dynein-dynactin-cargo adaptor complexes. Proc Natl Acad Sci U S A. 2017;114:E1597-E1606 pubmed publisher
    ..dynein movement that is activated by binding to the accessory complex dynactin and the cargo adaptor Bicaudal-D2 (BICD2). Mutations with the strongest effects on dynein motility in vitro are associated with MCD...
  24. Baffet A, Hu D, Vallee R. Cdk1 Activates Pre-mitotic Nuclear Envelope Dynein Recruitment and Apical Nuclear Migration in Neural Stem Cells. Dev Cell. 2015;33:703-16 pubmed publisher
    ..to the nuclear envelope (NE) specifically during G2 via two nuclear pore-mediated mechanisms involving RanBP2-BicD2 and Nup133-CENP-F. The mechanisms responsible for cell-cycle control of this behavior are unknown...
  25. Mosalaganti S, Keller J, Altenfeld A, Winzker M, Rombaut P, Saur M, et al. Structure of the RZZ complex and molecular basis of its interaction with Spindly. J Cell Biol. 2017;216:961-981 pubmed publisher
    ..We show that Spindly, a dynein adaptor, is related to BicD2 and binds RZZ directly in a farnesylation-dependent but membrane-independent manner...
  26. Unger A, Dekomien G, Güttsches A, Dreps T, Kley R, Tegenthoff M, et al. Expanding the phenotype of BICD2 mutations toward skeletal muscle involvement. Neurology. 2016;87:2235-2243 pubmed
    To expand the spectrum of bicaudal D, Drosophila, homologue 2 (BICD2) gene-related diseases, which so far includes autosomal dominant spinal muscular atrophy with lower extremity predominance 2 and hereditary spastic paraplegia due to ..
  27. Fritzler M, Hudson M, Choi M, Mahler M, Wang M, Bentow C, et al. Bicaudal D2 is a novel autoantibody target in systemic sclerosis that shares a key epitope with CENP-A but has a distinct clinical phenotype. Autoimmun Rev. 2018;17:267-275 pubmed publisher
    We studied the clinical correlations and epitopes of autoantibodies directed to a novel autoantigen, Bicaudal D (BICD2), in systemic sclerosis (SSc) and reviewed its relationship to centromere protein A (CENP-A)...
  28. Clift D, Schuh M. A three-step MTOC fragmentation mechanism facilitates bipolar spindle assembly in mouse oocytes. Nat Commun. 2015;6:7217 pubmed publisher
    ..First, PLK1 triggers a decondensation of the MTOC structure. Second, BicD2-anchored dynein stretches the MTOCs into fragmented ribbons along the nuclear envelope...
  29. Budzinska M, Wicher K, Terenzio M. Neuronal Roles of the Bicaudal D Family of Motor Adaptors. Vitam Horm. 2017;104:133-152 pubmed publisher
    ..Both mammalian BICD1 and BICD2 are highly expressed in the nervous system during development, and their importance in neuronal homeostasis has ..
  30. Jodoin J, Shboul M, Sitaram P, Zein Sabatto H, Reversade B, Lee E, et al. Human Asunder promotes dynein recruitment and centrosomal tethering to the nucleus at mitotic entry. Mol Biol Cell. 2012;23:4713-24 pubmed publisher
    ..In cultured human cells, this dynein pool is anchored to nuclear pore complexes through RanBP2-Bicaudal D2 (BICD2) and Nup133- centromere protein F (CENP-F) networks...
  31. Fuchs E, Short B, Barr F. Assay and properties of rab6 interaction with dynein-dynactin complexes. Methods Enzymol. 2005;403:607-18 pubmed
    ..Standard protocols for yeast two-hybrid analysis, and biochemical assays for the analysis of the interactions between Rab6, Bicaudal-D, and the subunits of the dynein-dynactin complex are outlined. ..
  32. Weiner O, Rentel M, Ott A, Brown G, Jedrychowski M, Yaffe M, et al. Hem-1 complexes are essential for Rac activation, actin polymerization, and myosin regulation during neutrophil chemotaxis. PLoS Biol. 2006;4:e38 pubmed
  33. Huynh W, Vale R. Disease-associated mutations in human BICD2 hyperactivate motility of dynein-dynactin. J Cell Biol. 2017;216:3051-3060 pubmed publisher
    Bicaudal D2 (BICD2) joins dynein with dynactin into a ternary complex (termed DDB) capable of processive movement...
  34. Holland P, Milne A, Garka K, Johnson R, Willis C, Sims J, et al. Purification, cloning, and characterization of Nek8, a novel NIMA-related kinase, and its candidate substrate Bicd2. J Biol Chem. 2002;277:16229-40 pubmed
    ..cloning, and characterization of human Nek8, a new mammalian NIMA-related kinase, and its candidate substrate Bicd2. Nek8 was isolated as a beta-casein kinase activity in rabbit lung and has an N-terminal catalytic domain ..
  35. Dharan A, Opp S, Abdel Rahim O, Keceli S, Imam S, Diaz Griffero F, et al. Bicaudal D2 facilitates the cytoplasmic trafficking and nuclear import of HIV-1 genomes during infection. Proc Natl Acad Sci U S A. 2017;114:E10707-E10716 pubmed publisher
    ..Here, we report that the dynein adapter protein bicaudal D2 (BICD2) is able to interact with HIV-1 viral cores in target cells...
  36. Oldmeadow C, Mossman D, Evans T, Holliday E, Tooney P, Cairns M, et al. Combined analysis of exon splicing and genome wide polymorphism data predict schizophrenia risk loci. J Psychiatr Res. 2014;52:44-9 pubmed publisher
    ..associated loci with a biologically plausible role in schizophrenia, including MCPH1, DLG3, ZC3H13, and BICD2, and additional loci that influence splicing of these genes, including YWHAH...
  37. Peeters K, Litvinenko I, Asselbergh B, Almeida Souza L, Chamova T, Geuens T, et al. Molecular defects in the motor adaptor BICD2 cause proximal spinal muscular atrophy with autosomal-dominant inheritance. Am J Hum Genet. 2013;92:955-64 pubmed publisher
    ..320C>T (p.Ser107Leu) mutation in bicaudal D homolog 2 (Drosophila) (BICD2)...
  38. Neveling K, Martínez Carrera L, Holker I, Heister A, Verrips A, Hosseini Barkooie S, et al. Mutations in BICD2, which encodes a golgin and important motor adaptor, cause congenital autosomal-dominant spinal muscular atrophy. Am J Hum Genet. 2013;92:946-54 pubmed publisher
    ..Here, we identified pathogenic variants in bicaudal D homolog 2 (Drosophila) (BICD2) in three families afflicted with autosomal-dominant SMA...
  39. Ambrogio C, Voena C, Manazza A, Piva R, Riera L, Barberis L, et al. p130Cas mediates the transforming properties of the anaplastic lymphoma kinase. Blood. 2005;106:3907-16 pubmed
  40. Jha R, Roostalu J, Cade N, Trokter M, Surrey T. Combinatorial regulation of the balance between dynein microtubule end accumulation and initiation of directed motility. EMBO J. 2017;36:3387-3404 pubmed publisher
    ..complex, they have opposite preferences for binding other regulators, either the adaptor protein Bicaudal-D2 (BicD2) or the multifunctional regulator Lissencephaly-1 (Lis1)...
  41. Storbeck M, Horsberg Eriksen B, Unger A, Holker I, Aukrust I, Martínez Carrera L, et al. Phenotypic extremes of BICD2-opathies: from lethal, congenital muscular atrophy with arthrogryposis to asymptomatic with subclinical features. Eur J Hum Genet. 2017;25:1040-1048 pubmed publisher
    ..in BICD cargo adapter 2 (BICD2) cause autosomal dominant spinal muscular atrophy, lower extremity-predominant 2 (SMALED2)...
  42. Rudnik Schöneborn S, Deden F, Eggermann K, Eggermann T, Wieczorek D, Sellhaus B, et al. Autosomal dominant spinal muscular atrophy with lower extremity predominance: A recognizable phenotype of BICD2 mutations. Muscle Nerve. 2016;54:496-500 pubmed publisher
    Heterozygous BICD2 gene mutations cause a form of autosomal dominant spinal muscular atrophy with lower extremity predominance (SMALED). We analyzed the BICD2 gene in a selected group of 25 index patients with neurogenic muscle atrophy...
  43. Matsuto M, Kano F, Murata M. Reconstitution of the targeting of Rab6A to the Golgi apparatus in semi-intact HeLa cells: A role of BICD2 in stabilizing Rab6A on Golgi membranes and a concerted role of Rab6A/BICD2 interactions in Golgi-to-ER retrograde transport. Biochim Biophys Acta. 2015;1853:2592-609 pubmed publisher
    ..Subsequent immunofluorescence analyses indicated decreased amounts of the GTP-bound active form of Rab6 in BICD2-knockdown cells...
  44. Novarino G, Fenstermaker A, Zaki M, Hofree M, Silhavy J, Heiberg A, et al. Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Science. 2014;343:506-511 pubmed publisher
    ..Our analysis links HSP to other neurodegenerative disorders and can facilitate gene discovery and mechanistic understanding of disease...
  45. Oates E, Rossor A, Hafezparast M, Gonzalez M, Speziani F, MacArthur D, et al. Mutations in BICD2 cause dominant congenital spinal muscular atrophy and hereditary spastic paraplegia. Am J Hum Genet. 2013;92:965-73 pubmed publisher
    ..We have identified four mutations in bicaudal D homolog 2 (Drosophila) (BICD2) in six kindreds affected by DCSMA, DCSMA with upper motor neuron features, or HSP...
  46. Fumoto K, Hoogenraad C, Kikuchi A. GSK-3beta-regulated interaction of BICD with dynein is involved in microtubule anchorage at centrosome. EMBO J. 2006;25:5670-82 pubmed
    ..These results imply that GSK-3beta may function in transporting centrosomal proteins to the centrosome by stabilizing the BICD1 and dynein complex, resulting in the regulation of a focused microtubule organization. ..
  47. Rossor A, Oates E, Salter H, Liu Y, Murphy S, Schule R, et al. Phenotypic and molecular insights into spinal muscular atrophy due to mutations in BICD2. Brain. 2015;138:293-310 pubmed publisher
    ..DYNC1H1, which encodes a microtubule motor protein in the dynein-dynactin complex and one of its cargo adaptors, BICD2. We have now identified 32 patients with BICD2 mutations from nine different families, providing detailed insights ..
  48. Splinter D, Razafsky D, Schlager M, Serra Marques A, Grigoriev I, Demmers J, et al. BICD2, dynactin, and LIS1 cooperate in regulating dynein recruitment to cellular structures. Mol Biol Cell. 2012;23:4226-41 pubmed publisher
    ..In this study, we focus on dynein-dynactin recruitment to cargo by the conserved motor adaptor Bicaudal D2 (BICD2)...