DOK7

Summary

Gene Symbol: DOK7
Description: docking protein 7
Alias: C4orf25, CMS10, CMS1B, protein Dok-7, downstream of tyrosine kinase 7
Species: human

Top Publications

  1. doi Clinical and molecular genetic findings in COLQ-mutant congenital myasthenic syndromes
    Violeta Mihaylova
    Friedrich Baur Institute, Department of Neurology, Ludwig Maximilians University, Munich, Germany
    Brain 131:747-59. 2008
  2. doi Congenital myasthenic syndromes and the formation of the neuromuscular junction
    David Beeson
    Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK
    Ann N Y Acad Sci 1132:99-103. 2008
  3. doi Phenotype genotype analysis in 15 patients presenting a congenital myasthenic syndrome due to mutations in DOK7
    A Ben Ammar
    Institut National de Neurologie, Universite Tunis El Manar, Tunis, Tunisia
    J Neurol 257:754-66. 2010
  4. doi Identification of previously unreported mutations in CHRNA1, CHRNE and RAPSN genes in three unrelated Italian patients with congenital myasthenic syndromes
    Raffaella Brugnoni
    Laboratory NBS Biotech, Fondazione Istituto Neurologico Carlo Besta, Milan, Italy
    J Neurol 257:1119-23. 2010
  5. ncbi Dok-7 mutations underlie a neuromuscular junction synaptopathy
    David Beeson
    Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK
    Science 313:1975-8. 2006
  6. pmc The cytoplasmic adaptor protein Dok7 activates the receptor tyrosine kinase MuSK via dimerization
    Elisa Bergamin
    Structural Biology Program, Kimmel Center for Biology and Medicine of the Skirball Institute and Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
    Mol Cell 39:100-9. 2010
  7. ncbi Variable phenotypes associated with mutations in DOK7
    Jennifer A Anderson
    Department of Neurology, University of California at Davis, Davis, CA 95618, USA
    Muscle Nerve 37:448-56. 2008
  8. ncbi The muscle protein Dok-7 is essential for neuromuscular synaptogenesis
    Kumiko Okada
    Department of Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113 8510, Japan
    Science 312:1802-5. 2006
  9. ncbi Phenotypical spectrum of DOK7 mutations in congenital myasthenic syndromes
    Juliane S Muller
    Friedrich Baur Institute, Department of Neurology, Ludwig Maximilians University, Munich, Germany
    Brain 130:1497-506. 2007
  10. ncbi Clinical features of the DOK7 neuromuscular junction synaptopathy
    Jacqueline Palace
    Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS, UK
    Brain 130:1507-15. 2007

Research Grants

  1. RICARDO ANIBAL MASELLI; Fiscal Year: 2014
  2. SIGNALING BY MUSK, A COMPONENT OF THE AGRIN RECEPTOR
    STEVEN BURDEN; Fiscal Year: 2012
  3. STEVEN BURDEN; Fiscal Year: 2015
  4. Role of DOK Proteins in Lung Cancer
    Masaru Niki; Fiscal Year: 2012
  5. Structure-Function Studies of the Receptor Tyrosine Kinase MuSK
    STEVAN HUBBARD; Fiscal Year: 2009
  6. STRUCTURAL STUDY OF THE INSULIN RECEPTOR TYROSINE KINASE
    Stevan R Hubbard; Fiscal Year: 2010

Scientific Experts

Detail Information

Publications80

  1. doi Clinical and molecular genetic findings in COLQ-mutant congenital myasthenic syndromes
    Violeta Mihaylova
    Friedrich Baur Institute, Department of Neurology, Ludwig Maximilians University, Munich, Germany
    Brain 131:747-59. 2008
    ..many patients had clinical features reminiscent of limb-girdle CMS with mutations in the recently discovered DOK7 gene, including sparing of eye movements and a predominantly proximal muscle weakness...
  2. doi Congenital myasthenic syndromes and the formation of the neuromuscular junction
    David Beeson
    Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK
    Ann N Y Acad Sci 1132:99-103. 2008
    ..Dok-7 binds MuSK and many of the mutations of DOK7 impair the MuSK signaling pathway...
  3. doi Phenotype genotype analysis in 15 patients presenting a congenital myasthenic syndrome due to mutations in DOK7
    A Ben Ammar
    Institut National de Neurologie, Universite Tunis El Manar, Tunis, Tunisia
    J Neurol 257:754-66. 2010
    ..Mutations of DOK7 have recently been described in recessive forms of CMS...
  4. doi Identification of previously unreported mutations in CHRNA1, CHRNE and RAPSN genes in three unrelated Italian patients with congenital myasthenic syndromes
    Raffaella Brugnoni
    Laboratory NBS Biotech, Fondazione Istituto Neurologico Carlo Besta, Milan, Italy
    J Neurol 257:1119-23. 2010
    ..The alphaG378D mutation was recessive, but recessive CHRNA1 mutations have rarely been reported previously, so studies on the effect of this mutation at the cellular level would be of interest...
  5. ncbi Dok-7 mutations underlie a neuromuscular junction synaptopathy
    David Beeson
    Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK
    Science 313:1975-8. 2006
    ..We showed that recessive inheritance of mutations in Dok-7, which result in a defective structure of the neuromuscular junction, is a cause of CMS with proximal muscle weakness...
  6. pmc The cytoplasmic adaptor protein Dok7 activates the receptor tyrosine kinase MuSK via dimerization
    Elisa Bergamin
    Structural Biology Program, Kimmel Center for Biology and Medicine of the Skirball Institute and Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
    Mol Cell 39:100-9. 2010
    ..and the following muscle proteins: LRP4, the receptor for Agrin; MuSK, a receptor tyrosine kinase (RTK); and Dok7 (or Dok-7), a cytoplasmic adaptor protein...
  7. ncbi Variable phenotypes associated with mutations in DOK7
    Jennifer A Anderson
    Department of Neurology, University of California at Davis, Davis, CA 95618, USA
    Muscle Nerve 37:448-56. 2008
    ..with the limb-girdle variant of congenital myasthenic syndrome (CMS) possess mutations in the human Dok-7 gene (DOK7). We identified six unrelated CMS patients with DOK7 mutations...
  8. ncbi The muscle protein Dok-7 is essential for neuromuscular synaptogenesis
    Kumiko Okada
    Department of Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113 8510, Japan
    Science 312:1802-5. 2006
    ..Mice lacking Dok-7 formed neither acetylcholine receptor clusters nor neuromuscular synapses. Thus, Dok-7 is essential for neuromuscular synaptogenesis through its interaction with MuSK...
  9. ncbi Phenotypical spectrum of DOK7 mutations in congenital myasthenic syndromes
    Juliane S Muller
    Friedrich Baur Institute, Department of Neurology, Ludwig Maximilians University, Munich, Germany
    Brain 130:1497-506. 2007
    ..Subsequently, we and others identified mutations in DOK7 as a cause of congenital myasthenic syndromes (CMS), providing evidence for a crucial role of Dok-7 in maintaining ..
  10. ncbi Clinical features of the DOK7 neuromuscular junction synaptopathy
    Jacqueline Palace
    Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS, UK
    Brain 130:1507-15. 2007
    Mutations in DOK7 have recently been shown to underlie a recessive congenital myasthenic syndrome (CMS) associated with small simplified neuromuscular junctions ('synaptopathy') but normal acetylcholine receptor and acetylcholinesterase ..
  11. pmc Dok-7 myasthenia: phenotypic and molecular genetic studies in 16 patients
    Duygu Selcen
    Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN 55905, USA
    Ann Neurol 64:71-87. 2008
    ..Detailed analysis of phenotypic and molecular genetic aspects of Dok-7 myasthenia in 16 patients...
  12. doi The carboxyl-terminal region of Dok-7 plays a key, but not essential, role in activation of muscle-specific receptor kinase MuSK and neuromuscular synapse formation
    Ryo Ueta
    Division of Genetics, Department of Cancer Biology
    J Biochem . 2017
    ..Dok-7 is the essential cytoplasmic activator of MuSK, and indeed mice lacking Dok-7 form no NMJs. Moreover, DOK7 gene mutations underlie DOK7 myasthenia, an NMJ synaptopathy...
  13. doi Prenatal diagnosis and genetic analysis of fetal akinesia deformation sequence and multiple pterygium syndrome associated with neuromuscular junction disorders: a review
    Chih Ping Chen
    Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
    Taiwan J Obstet Gynecol 51:12-7. 2012
    ..Genetic analysis of mutations in the neuromuscular junction genes such as CHRNA1, CHRND, CHRNG, CNTN1, DOK7, RAPSN, and SYNE1 may unveil the pathogenetic cause of fetal akinesia deformation sequence and multiple pterygium ..
  14. pmc Salbutamol-responsive limb-girdle congenital myasthenic syndrome due to a novel missense mutation and heteroallelic deletion in MUSK
    Constanze Gallenmüller
    Friedrich Baur Institut, Ludwig Maximilians University, Munich, Germany
    Neuromuscul Disord 24:31-5. 2014
    ..Our findings highlight the importance of a molecular diagnosis in CMS and demonstrate considerable similarities between patients with MUSK and DOK7-related CMS in terms of clinical phenotype and treatment options.
  15. pmc LRP4 third β-propeller domain mutations cause novel congenital myasthenia by compromising agrin-mediated MuSK signaling in a position-specific manner
    Bisei Ohkawara
    Division of Neurogenetics, Center for Neurological Diseases and Cancer and
    Hum Mol Genet 23:1856-68. 2014
    ..We conclude that LRP4 is a new CMS disease gene and that the 3rd beta propeller domain of LRP4 mediates the two signaling pathways in a position-specific manner. ..
  16. doi Pharmacologic treatment of downstream of tyrosine kinase 7 congenital myasthenic syndrome
    Nanna Witting
    Neuromuscular Research Unit, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
    JAMA Neurol 71:350-4. 2014
    ..Congenital myasthenic syndromes (CMSs) are increasingly recognized as causes of muscle fatigue and weakness. However, treatment of individual syndromes has been described only in small case series...
  17. pmc Identification of a Dutch founder mutation in MUSK causing fetal akinesia deformation sequence
    M Brigita Tan-Sindhunata
    Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands
    Eur J Hum Genet 23:1151-7. 2015
    ..FADS can result from mutations in CHRNG, CHRNA1, CHRND, DOK7 and RAPSN; however, these genes only account for a minority of cases...
  18. doi Exercise training alters DNA methylation patterns in genes related to muscle growth and differentiation in mice
    Timo Kanzleiter
    Department of Experimental Diabetology, German Institute of Human Nutrition, Potsdam Rehbruecke, Germany German Center for Diabetes Research DZD, Neuherberg, Germany and
    Am J Physiol Endocrinol Metab 308:E912-20. 2015
    ..factors (Plexin A2) as well as genes that participate in muscle hypertrophy (Igfbp4) and motor neuron innervation (Dok7)...
  19. ncbi Limb girdle weakness responding to salbutamol: an Indian family with DOK7 mutation
    S Khadilkar
    Department of Neurology, Grant Government Medical College and JJ Hospital, Mumbai, India and Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Atlanta, Georgia, 30322, USA Correspondence to Prof Satish Khadilkar, 110, New Wing, First Floor, Bombay Hospital, 12, New Marine Lines, Mumbai 400 020, India
    Indian Pediatr 52:243-4. 2015
    ..Congenital Myasthenic Syndromes (CMS) are heterogeneous genetic diseases...
  20. doi DNA methylation as a promising landscape: A simple blood test for breast cancer prediction
    Golnaz Khakpour
    Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
    Tumour Biol 36:4905-12. 2015
    ..for predisposition to breast cancer, leading to suggest that ATM, TITF1, SFRP1, NUP155, NEUROD1, ZNF217, DBC2, DOK7 and ESR1 genes and the LINE1, Alu and Sat2 DNA elements could be considered as the potential epimarkers...
  21. pmc Protein kinase CK2 interacts at the neuromuscular synapse with Rapsyn, Rac1, 14-3-3γ, and Dok-7 proteins and phosphorylates the latter two
    Dustin Herrmann
    From the Institut für Biochemie, Friedrich Alexander Universitat Erlangen Nurnberg, Fahrstrasse 17, D 91054 Erlangen, Germany
    J Biol Chem 290:22370-84. 2015
    ..Additionally, we mapped the interacting epitopes of all four binding partners to CK2 and thereby gained insights into the potential role of the CK2/Rapsyn interaction. ..
  22. pmc Global N-linked Glycosylation is Not Significantly Impaired in Myoblasts in Congenital Myasthenic Syndromes Caused by Defective Glutamine-Fructose-6-Phosphate Transaminase 1 (GFPT1)
    Qiushi Chen
    Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK
    Biomolecules 5:2758-81. 2015
    ..controls, three GFPT1 patients, and four patients with other muscular diseases, namely CMS caused by mutations in DOK7, myopathy caused by mutations in MTND5, limb girdle muscular dystrophy type 2A (LGMD2A), and Pompe disease...
  23. doi Effective Treatment With Albuterol in DOK7 Congenital Myasthenic Syndrome in Children
    Chang Yong Tsao
    Nationwide Children s Hospital, The Ohio State University, Columbus, Ohio Electronic address
    Pediatr Neurol 54:85-7. 2016
    ..DOK7 (downstream of tyrosine kinase 7) congenital myasthenic syndrome was previously treated successfully with ephedrine and salbutamol; ..
  24. doi Anticholinesterase Therapy Worsening Head Drop and Limb Weakness Due to a Novel DOK7 Mutation
    Dominika Lozowska
    Department of Neurology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO Prevention Genetics, Marshfield, WI and Invitae Corporation, San Francisco, CA
    J Clin Neuromuscul Dis 17:72-7. 2015
    Dok-7 myasthenia is an autosomal recessive congenital myasthenic syndrome due to DOK7 mutations...
  25. pmc Congenital Myasthenic Syndromes with Predominant Limb Girdle Weakness
    Teresinha Evangelista
    John Walton Muscular Dystrophy Research Centre, MRC Centre for Neuromuscular Diseases, Newcastle University, Newcastle upon Tyne, UK
    J Neuromuscul Dis 2:S21-S29. 2015
    ..LG-CMS are inherited in autosomal recessive traits, and are often associated with mutations in DOK7 and GFPT1, and less frequently with mutations in COLQ, ALG2, ALG14 and DPAGT...
  26. doi Postnatal knockdown of dok-7 gene expression in mice causes structural defects in neuromuscular synapses and myasthenic pathology
    Takahiro Eguchi
    Division of Genetics, Department of Cancer Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, 108 8639, Japan
    Genes Cells 21:670-6. 2016
    ..Indeed, mice lacking either Dok-7 or MuSK form no NMJs, and defects in the human DOK7 gene underlie a congenital myasthenic syndrome (an NMJ disorder)...
  27. pmc Multiscale Simulations Suggest a Mechanism for the Association of the Dok7 PH Domain with PIP-Containing Membranes
    Amanda Buyan
    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    PLoS Comput Biol 12:e1005028. 2016
    b>Dok7 is a peripheral membrane protein that is associated with the MuSK receptor tyrosine kinase. Formation of the Dok7/MuSK/membrane complex is required for the activation of MuSK...
  28. doi Silencing of Dok-7 in Adult Rat Muscle Increases Susceptibility to Passive Transfer Myasthenia Gravis
    Alejandro M Gomez
    Neuroimmunology Group, Division of Neuroscience, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands Electronic address
    Am J Pathol 186:2559-68. 2016
    ..These results suggest that a reduced expression of Dok-7 may play a role in the susceptibility to passive transfer MG, by rendering AChR clusters less resistant to the autoantibody attack. ..
  29. pmc Congenital myasthenic syndrome in Israel: Genetic and clinical characterization
    Sharon Aharoni
    Institute of Child Neurology, Schneider Children s Medical Center of Israel, Petach Tikva, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Electronic address
    Neuromuscul Disord . 2016
    ..Mutations in CHRNE were identified in 7 kinships. Less commonly detected mutations were in CHRND, CHAT, GFPT1 and DOK7. In conclusion, mutations in RAPSN and COLQ are the most common causes of CMS in our cohort...
  30. doi Divalent and monovalent autoantibodies cause dysfunction of MuSK by distinct mechanisms in a rabbit model of myasthenia gravis
    Shuuichi Mori
    Department of Geriatric Medicine, Tokyo Metropolitan Institute of Gerontology, Tokyo 173 0015, Japan
    J Neuroimmunol 244:1-7. 2012
    ..Taken together, these findings suggest that complement activation is not necessary for the MG onset and that both divalent and monovalent antibodies may cause MG in vivo by inducing MuSK dysfunction...
  31. pmc A mutation causes MuSK reduced sensitivity to agrin and congenital myasthenia
    Asma Ben Ammar
    INSERM, UMRS 975, UPMC, institut du cerveau et de la moelle épinière, Groupe Hospitalier Pitie Salpetriere, Paris, France
    PLoS ONE 8:e53826. 2013
    ..In vitro experiments showed that the mutation alters agrin-dependent acetylcholine receptor aggregation, causes a constitutive activation of MuSK and a decrease in its agrin- and Dok-7-dependent phosphorylation...
  32. doi Synaptic dysfunction in congenital myasthenic syndromes
    David Beeson
    Weatherall Institute of Molecular Medicine, The John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom
    Ann N Y Acad Sci 1275:63-9. 2012
    ..of the methods that can be used to define if a DNA sequence variant is pathogenic with reference to variants in DOK7. We highlight a new mechanism for disruption of AChR function, where a mutation in the AChR ɛ-subunit gene causes ..
  33. doi DOK7 congenital myasthenic syndrome
    Jacqueline Palace
    Clinical Neurology, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, United Kingdom
    Ann N Y Acad Sci 1275:49-53. 2012
    Despite being a fairly recent discovery, DOK7 congenital myasthenic syndrome (CMS) is the third most common form of CMS in the United Kingdom. DOK7 is a postsynaptic protein associated with the AChR clustering pathway...
  34. doi Structure of the neuromuscular junction: function and cooperative mechanisms in the synapse
    Masaharu Takamori
    Neurological Center, Kanazawa Nishi Hospital, Japan
    Ann N Y Acad Sci 1274:14-23. 2012
    ..and receptor tyrosine kinases; (2) postsynaptic acetylcholine receptor clustering mediated by the muscle-specific, Dok7-stimulated tyrosine kinase (MuSK) through two signaling mechanisms: one via agrin-Lrp4-MuSK (Ig1/2 domains) and the ..
  35. doi Salbutamol benefits children with congenital myasthenic syndrome due to DOK7 mutations
    Georgina Burke
    Wessex Neurological Centre, Southampton General Hospital, Southampton, UK
    Neuromuscul Disord 23:170-5. 2013
    Congenital myasthenic syndromes due to DOK7 mutations cause fatigable limb girdle weakness. Treatment with ephedrine improves muscle strength...
  36. ncbi [Congenital myasthenic syndromes]
    Kinji Ohno
    Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine
    Rinsho Shinkeigaku 52:1159-61. 2012
    ..In the past two years, we diagnosed 15 cases with CMS in Japan, and identified mutations in 12 patients. All the mutations except for one are unique to Japanese patients. We assume that more CMS cases still remain undiagnosed in Japan...
  37. doi Pregnancy in congenital myasthenic syndrome
    L Servais
    Service of therapeutic trials and databases, Institut de Myologie, Groupe Hospitalier Pitie Salpetriere, Paris, France
    J Neurol 260:815-9. 2013
    ..We report on 17 pregnancies in eight patients with CMS with mutations in CHRNA1, CHRNE, CHRND, GFPT1, COLQ, or DOK7. Symptoms worsened for six patients during at least one of their pregnancies, and one patient required ..
  38. pmc DNA methylation profiling in breast cancer discordant identical twins identifies DOK7 as novel epigenetic biomarker
    Holger Heyn
    Cancer Epigenetics and Biology Program PEBC, Bellvitge Biomedical Research Institute IDIBELL, L Hospitalet, Barcelona, Catalonia 08907, Spain
    Carcinogenesis 34:102-8. 2013
    ..Confirming the results in an independent validation cohort of 21 twin pairs determined the docking protein DOK7 as a candidate for blood-based cancer diagnosis...
  39. doi DOK7 limb-girdle myasthenic syndrome mimicking congenital muscular dystrophy
    Ibrahim Mahjneh
    Department of Neurology, University of Oulu, Oulu, Finland
    Neuromuscul Disord 23:36-42. 2013
    ..3. As the DOK7 gene is located in this genetic interval, we considered it a potential candidate for this condition...
  40. doi The spectrum of mutations that underlie the neuromuscular junction synaptopathy in DOK7 congenital myasthenic syndrome
    Judith Cossins
    Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK
    Hum Mol Genet 21:3765-75. 2012
    ..A subgroup of CMS patients have a recessively inherited limb-girdle pattern of weakness caused by mutations in DOK7. DOK7 encodes DOK7, an adaptor protein that is expressed in the skeletal muscle and heart and that is essential for ..
  41. doi [Congenital myasthenic syndromes: difficulties in the diagnosis, course and prognosis, and therapy--The French National Congenital Myasthenic Syndrome Network experience]
    B Eymard
    Centre de référence des affections neuromusculaires Paris Est, Service de neurologie 2, Institut de Myologie, Hopital de la Pitie Salpetriere, 47 bd de l Hopital, 75013 Paris, France
    Rev Neurol (Paris) 169:S45-55. 2013
    ..prognosis of CMS was studied in a series of 79 patients recruited with the following gene mutations: CHRNA; CHRNE; DOK7; COLQ; RAPSN; AGRN; and MUSK...
  42. doi Congenital myasthenic syndrome: a brief review
    Paulo José Lorenzoni
    Neuromuscular Disorders Unit, Division of Neurology, Department of Internal Medicine, Hospital de Clinicas da Universidade Federal do Parana, Curitiba, PR, Brazil
    Pediatr Neurol 46:141-8. 2012
    ..may be necessary to identify specific mutations in CHAT, COLQ, LAMB2, CHRNA, CHRNB, CHRND, CHRNE, CHRNG, RAPSN, DOK7, MUSK, AGRN, SCN4A, GFPT1, or PLEC1 genes...
  43. doi Activation of receptor protein-tyrosine kinases from the cytoplasmic compartment
    Yuji Yamanashi
    Division of Genetics, Department of Cancer Biology, The Institute of Medical Science, The University of Tokyo, Tokyo 108 8639, Japan
    J Biochem 151:353-9. 2012
    ..Given that failure of Dok-7 signaling causes myasthenia, and inhibition of cytohesin signaling reduces the proliferation of EGFR-dependent cancer cells, cytoplasmic activators of RTKs may provide new therapeutic targets...
  44. pmc Current status of the congenital myasthenic syndromes
    Andrew G Engel
    Department of Neurology, Mayo Clinic, Rochester, MN 55905, United States
    Neuromuscul Disord 22:99-111. 2012
    ..4, the muscle specific protein kinase (MuSK), agrin, downstream of tyrosine kinase 7 (Dok-7), and glutamine-fructose-6-phosphate transaminase 1 (GFPT1)...
  45. pmc Structure and activation of MuSK, a receptor tyrosine kinase central to neuromuscular junction formation
    Stevan R Hubbard
    Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA Electronic address
    Biochim Biophys Acta 1834:2166-9. 2013
    ..In addition, Dok7, a cytoplasmic adaptor protein, is also required for MuSK activation in vivo...
  46. doi Congenital myasthenic syndrome with tubular aggregates caused by GFPT1 mutations
    Velina Guergueltcheva
    Department of Neurology, Friedrich Baur Institut, Ludwig Maximilians University, Munich, Germany
    J Neurol 259:838-50. 2012
    ..b>DOK7 mutations have been identified as causing the disorder in about half of the cases...
  47. pmc Endosomal trafficking of the receptor tyrosine kinase MuSK proceeds via clathrin-dependent pathways, Arf6 and actin
    Susan Luiskandl
    Center for Brain Research, Medical University of Vienna, Vienna, Austria
    FEBS J 280:3281-97. 2013
    ..MuSK activation by Dok7 mildly affects the localization of MuSK on the cell surface but has no effect on the rate of MuSK internalization...
  48. pmc The role of MuSK in synapse formation and neuromuscular disease
    Steven J Burden
    Molecular Neurobiology Program, Helen L and Martin S Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, NYU Medical School, New York, NY 10016, USA
    Cold Spring Harb Perspect Biol 5:a009167. 2013
    ..Mutations in MuSK and in genes that function in the MuSK signaling pathway, including Dok-7, cause congenital myasthenia, and autoantibodies to MuSK, Lrp4, and acetylcholine receptors are responsible for myasthenia gravis...
  49. doi Salbutamol therapy in congenital myasthenic syndrome due to DOK7 mutation
    Paulo J Lorenzoni
    Neurology Division, Internal Medicine Department, Hospital de Clinicas, Universidade Federal do Parana, Curitiba, PR, Brazil
    J Neurol Sci 331:155-7. 2013
    ..In this study, we analyzed the effect of salbutamol in five patients with Dok-7 CMS...
  50. doi A mouse model of the slow channel myasthenic syndrome: Neuromuscular physiology and effects of ephedrine treatment
    R G Webster
    Neurosciences Group, Nuffield Dept of Clinical Neurosciences, University of Oxford, Oxford, UK
    Exp Neurol 248:286-98. 2013
    ..Ephedrine and salbutamol show clear benefit when used in the treatment of DOK7 or COLQ congenital myasthenic syndromes...
  51. doi DOK7 congenital myasthenic syndrome in childhood: early diagnostic clues in 23 children
    Andrea Klein
    Department of Paediatric Neurology, University Children s Hospital, Zurich, Switzerland Dubowitz Neuromuscular Centre, Institute of Child Health and Great Ormond Street Hospital, London, UK Electronic address
    Neuromuscul Disord 23:883-91. 2013
    Mutations in DOK7 are a common cause of congenital myasthenia. Treatment with ephedrine or salbutamol is effective, but diagnosis is often delayed...
  52. pmc MuSK myasthenia gravis IgG4 disrupts the interaction of LRP4 with MuSK but both IgG4 and IgG1-3 can disperse preformed agrin-independent AChR clusters
    Inga Koneczny
    Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom
    PLoS ONE 8:e80695. 2013
    ..receptor-related protein-4 (LRP4), which then binds to MuSK; MuSK interaction with the intracellular protein Dok7 results in clustering of the acetylcholine receptors (AChRs) on the postsynaptic membrane...
  53. doi Dok-7 promotes slow muscle integrity as well as neuromuscular junction formation in a zebrafish model of congenital myasthenic syndromes
    Juliane S Muller
    Institute of Human Genetics, International Centre for Life, Newcastle University, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK
    Hum Mol Genet 19:1726-40. 2010
    ..smaller than in the wild-type zebrafish, reminiscent of the neuromuscular endplate pathology seen in patients with DOK7 mutations...
  54. ncbi Structural factors influencing the efficacy of neuromuscular transmission
    Clarke R Slater
    Institute of Neuroscience, Faculty of Medical Sciences, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne NE2 4HH, UK
    Ann N Y Acad Sci 1132:1-12. 2008
    ..This condition emphasizes the importance of structural features in achieving reliability of neuromuscular transmission...
  55. doi The roles of Dok family adapters in immunoreceptor signaling
    Ryuichi Mashima
    Division of Genetics, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
    Immunol Rev 232:273-85. 2009
    ..Here, we review the physiological roles and underlying mechanisms of Dok family proteins...
  56. doi Ephedrine therapy in eight patients with congenital myasthenic syndrome due to DOK7 mutations
    U Schara
    Dept of Pediatric Neurology, University of Essen, Germany
    Neuromuscul Disord 19:828-32. 2009
    In congenital myasthenic syndrome with DOK7 mutations ephedrine was reported to be beneficial in single patients. We carried out a small, open and prospective cohort study in eight European patients manifesting from birth to 12 years...
  57. doi Germline mutation in DOK7 associated with fetal akinesia deformation sequence
    J Vogt
    Department of Medical and Molecular Genetics and WellChild Paediatric Research Centre, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK
    J Med Genet 46:338-40. 2009
    ....
  58. doi Dok-7 activates the muscle receptor kinase MuSK and shapes synapse formation
    Akane Inoue
    Division of Genetics and Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Tokyo 108 8639, Japan
    Sci Signal 2:ra7. 2009
    ..These observations indicate that Dok-7 positively regulates neuromuscular synaptogenesis by controlling MuSK activity, its distribution, and its responsiveness to neural agrin...
  59. pmc Dok-7/MuSK signaling and a congenital myasthenic syndrome
    Y Yamanashi
    Division of Genetics, Department of Cancer Biology, The Institute of Medical Science, The University of Tokyo, Japan
    Acta Myol 27:25-9. 2008
    ..b>DOK7 has been found to be a major locus for mutations that underlie a genetic form of myasthenia with a characteristic '..
  60. pmc A mammalian homolog of Drosophila tumorous imaginal discs, Tid1, mediates agrin signaling at the neuromuscular junction
    Jenny Linnoila
    Molecular Pharmacology Graduate Training Program, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    Neuron 60:625-41. 2008
    ..These results demonstrate that Tid1 is an essential component of the agrin signaling pathway, crucial for synaptic development...
  61. doi Congenital myasthenic syndromes in childhood: diagnostic and management challenges
    M Kinali
    The Dubowitz Neuromuscular Centre, Great Ormond Street Hospital and Institute of Child Health, University College, London, UK
    J Neuroimmunol 201:6-12. 2008
    ..Mutations have been identified so far in 32/46 children: 10 RAPSN, 7 COLQ, 6 CHRNE, 7 DOK7, 1 CHRNA1 and 1 CHAT...
  62. pmc Further observations in congenital myasthenic syndromes
    Andrew G Engel
    Department of Neurology and Muscle Research Laboratory, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    Ann N Y Acad Sci 1132:104-13. 2008
    ..4, MuSK, and Dok-7. Moreover, emerging genotype-phenotype correlations are providing clues for targeted mutation analysis. This review focuses on the recent observations in selected CMS...
  63. ncbi [Overview: MuSK/Dok-7]
    Masakatsu Motomura
    The First Department of Internal Medicine, Graduate School of Biomedical Sciences, Nagasaki University
    Nihon Rinsho 66:1140-8. 2008
    ..Subsequently, mutations in Dok-7 as a cause of CMS were identified, providing evidence for a crucial role of Dok-7 in maintaining synaptic structure. Their effect on MuSK/Dok -7 function needs to be explored...
  64. doi Mutations causing DOK7 congenital myasthenia ablate functional motifs in Dok-7
    Johko Hamuro
    Department of Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo ku, Yushima, Tokyo 113 8510, Japan
    J Biol Chem 283:5518-24. 2008
    ..Both Dok-7 and MuSK are required for neuromuscular synaptogenesis. Mutations in DOK7 underlie a congenital myasthenic syndrome (CMS) associated with small and simplified neuromuscular synapses likely ..
  65. pmc Downstream of tyrosine kinase/docking protein 6, as a novel substrate of tropomyosin-related kinase C receptor, is involved in neurotrophin 3-mediated neurite outgrowth in mouse cortex neurons
    Wei Qi Li
    National Key Laboratory of Medical Molecular Biology, School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China
    BMC Biol 8:86. 2010
    The downstream of tyrosine kinase/docking protein (Dok) adaptor protein family has seven members, Dok1 to Dok7, that act as substrates of multiple receptor tyrosine kinase and non-receptor tyrosine kinase...
  66. pmc Mutations in MUSK causing congenital myasthenic syndrome impair MuSK-Dok-7 interaction
    Ricardo A Maselli
    Department of Neurology, School of Veterinary Medicine, University of California Davis, Davis, CA 95618, USA
    Hum Mol Genet 19:2370-9. 2010
    ....
  67. pmc Ephedrine treatment in congenital myasthenic syndrome due to mutations in DOK7
    D Lashley
    Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK
    Neurology 74:1517-23. 2010
    ..Patients usually do not respond to or worsen with the standard CMS treatments: cholinesterase inhibitors and 3,4-diaminopyridine. However, anecdotal reports suggest they may improve with ephedrine...
  68. pmc Congenital myasthenic syndromes in 2012
    Andrew G Engel
    Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
    Curr Neurol Neurosci Rep 12:92-101. 2012
    ..4, muscle-specific kinase, agrin, β2-laminin, downstream of tyrosine kinase 7, and glutamine-fructose-6-phosphate transaminase 1...
  69. pmc Beneficial effects of albuterol in congenital endplate acetylcholinesterase deficiency and Dok-7 myasthenia
    Teerin Liewluck
    Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, Minnesota 55905, USA
    Muscle Nerve 44:789-94. 2011
    ..EP AChE, Dok-7, and β(2)-laminin deficiencies respond favorably to ephedrine, but ephedrine can no longer be prescribed in the USA...
  70. ncbi [Genetic defects and disorders at the neuromuscular junction]
    Kinji Ohno
    Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan
    Brain Nerve 63:669-78. 2011
    ..Acetylcholinesterase is inhibited by the nerve gas sarin and by organophosphate pesticides. This review focuses on the molecular bases underlying defects of AChR, rapsyn, Nav1.4, collagen Q, and choline acetyltransferase...
  71. ncbi [Molecular mechanisms underlying the formation of neuromuscular junction]
    Osamu Higuchi
    Division of Genetics, Department of Cancer Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
    Brain Nerve 63:649-55. 2011
    ..Moreover, new evidence indicates that cyclin-dependent kinase 5 (Cdk5) regulates postsynaptic differentiation. In this review, we summarize the latest developments in molecular mechanisms underlying NMJ formation in vertebrates...
  72. doi The transcription factor Sp1 plays a crucial role in dok-7 gene expression
    Johko Hamuro
    Department of Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, 1 5 45 Yushima, Bunkyo ku, Tokyo 113 8510, Japan
    Biochem Biophys Res Commun 408:293-9. 2011
    ..Mutations of the human DOK7 gene underlie a limb-girdle type of congenital myasthenic syndrome, a group of disorders characterized by NMJ ..
  73. doi Investigation for RAPSN and DOK-7 mutations in a cohort of seronegative myasthenia gravis patients
    Espen Homleid Alseth
    Department of Clinical Medicine, University of Bergen, Bergen, Norway
    Muscle Nerve 43:574-7. 2011
    ..Because late-onset congenital myasthenic syndromes (CMSs) due to RAPSN or DOK7 mutations may be mistaken for SNMG, we investigated their frequency in a nationwide SNMG cohort.
  74. doi MuSK levels differ between adult skeletal muscles and influence postsynaptic plasticity
    Anna R Punga
    Department of Neurobiology Pharmacology, Biozentrum, University of Basel, Basel, Switzerland
    Eur J Neurosci 33:890-8. 2011
    ..We believe that these findings are important for our understanding of adult muscle plasticity and the selective muscle involvement in neuromuscular disorders in which MuSK is diminished...
  75. pmc Dok-7 regulates neuromuscular synapse formation by recruiting Crk and Crk-L
    Peter T Hallock
    Molecular Neurobiology Program, Skirball Institute of Biomolecular Medicine, New York University Medical School, New York, New York 10016, USA
    Genes Dev 24:2451-61. 2010
    ....
  76. ncbi Motor endplate remodeling in some cases with congenital myasthenic syndrome
    Anna Fidzianska
    Neuromuscular Unit, Medical Centre, Polish Academy of Science, Pawinskiego 5, 02 106 Warsaw, Poland
    Folia Neuropathol 48:200-5. 2010
    ..The conjunction of postsynaptic membrane paucity and its degeneration was a specific structural feature observed in the third syndrome with no established genetic defects...
  77. doi DOK7 mutations presenting as a proximal myopathy in French Canadians
    Myriam Srour
    Laboratoire de neurogénétique de la motricité, Centre de Recherche du CHUM, Montreal, Universite de Montreal, QC, Canada
    Neuromuscul Disord 20:453-7. 2010
    b>DOK7 mutations cause a congenital myasthenic syndrome (OMIM 254300) characterized by a "limb-girdle" phenotype. We identified 7 French-Canadian patients with a previously undiagnosed proximal myopathy. A genome wide scan was performed...
  78. doi Congenital stridor with feeding difficulty as a presenting symptom of Dok7 congenital myasthenic syndrome
    Chris G Jephson
    Department of Otolaryngology, Great Ormond Street Hospital for Children and Institute of Child Health, Great Ormond Street, London, WC1N 3JH, UK
    Int J Pediatr Otorhinolaryngol 74:991-4. 2010
    ..from birth, but diagnosis is often delayed for several years, notably in post-synaptic CMS due to mutations in the DOK7 gene...

Research Grants6

  1. RICARDO ANIBAL MASELLI; Fiscal Year: 2014
    ..CHAT), rapsyn (RAPSN), the voltage-gated muscle sodium channel (SCN4A), the muscle-specific kinase (MUSK), Dok-7 (DOK7) and the fetal subunit of the AChR (CHRNG), have been demonstrated to be implicated in the pathogenesis of other ..
  2. SIGNALING BY MUSK, A COMPONENT OF THE AGRIN RECEPTOR
    STEVEN BURDEN; Fiscal Year: 2012
    ..The experiments described here are designed to determine how Lrp4 and Dok-7, two newly discovered components of this signaling pathway mediate Agrin responsiveness, lead to MuSK phosphorylation and stimulate synaptic differentiation. ..
  3. STEVEN BURDEN; Fiscal Year: 2015
    ..Moreover, mutations in genes that are downstream from Crk/Crk-L may likewise cause congenital myasthenia, so identifying the pathway downstream from Crk/Crk-L may reveal new genes responsible for congenital myasthenia. ..
  4. Role of DOK Proteins in Lung Cancer
    Masaru Niki; Fiscal Year: 2012
    ..In addition, we will extend these data to humans and attempt to identify human BASCs and determine if they express Dok proteins. ..
  5. Structure-Function Studies of the Receptor Tyrosine Kinase MuSK
    STEVAN HUBBARD; Fiscal Year: 2009
    ..By revealing the biochemical mechanisms underlying the formation of this important synapse, we will better understand, at a molecular level, how defects in this process give rise to neuromuscular disorders. ..
  6. STRUCTURAL STUDY OF THE INSULIN RECEPTOR TYROSINE KINASE
    Stevan R Hubbard; Fiscal Year: 2010
    ..By understanding at the molecular level how the insulin receptor is regulated, we hope to facilitate efforts to design small-molecule agonists and inhibitors that could potentially be used as anti-diabetic therapeutics. ..