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PMID: 9707615 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

ATM binds to beta-adaptin in cytoplasmic vesicles.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 17 ·1998-08-18 ·Pages 10146-51

Lim DS, Kirsch DG, Canman CE, Ahn JH, Ziv Y, Newman LS, Darnell RB, Shiloh Y, Kastan MB

Abstract

Inherited mutations in the ATM gene lead to a complex clinical phenotype characterized by neuronal degeneration, oculocutaneous telangiectasias, immune dysfunction, and cancer predisposition. Using the yeast two-hybrid system, we demonstrate that ataxia telangiectasia mutated (ATM) binds to beta-adaptin, one of the components of the AP-2 adaptor complex, which is involved in clathrin-mediated endocytosis of receptors. The interaction between ATM and beta-adaptin was confirmed in vitro, and coimmunoprecipitation and colocalization studies show that the proteins also associate in vivo. ATM also interacts in vitro with beta-NAP, a neuronal-specific beta-adaptin homolog that was identified as an autoantigen in a patient with cerebellar degeneration. Our data describing the association of ATM with beta-adaptin in vesicles indicate that ATM may play a role in intracellular vesicle and/or protein transport mechanisms.

MeSH Terms
Adaptor Protein Complex 3 Adaptor Protein Complex beta Subunits Animals Ataxia Telangiectasia/etiology,genetics,metabolism Ataxia Telangiectasia Mutated Proteins Autoantigens/metabolism Base Sequence Cell Cycle Proteins Cerebellum/immunology,metabolism,pathology Chlorocebus aethiops Cytoplasm/metabolism DNA Primers/genetics DNA-Binding Proteins Humans In Vitro Techniques Membrane Proteins/metabolism Mice Nerve Tissue Proteins/immunology,metabolism Peptide Fragments/genetics,metabolism Phosphoproteins/immunology,metabolism Protein Binding Protein Serine-Threonine Kinases Proteins/genetics,metabolism Saccharomyces cerevisiae/genetics,metabolism Transfection Tumor Suppressor Proteins Vero Cells
Chemicals
AP3B2 protein, human Adaptor Protein Complex 3 Adaptor Protein Complex beta Subunits Autoantigens Cell Cycle Proteins DNA Primers DNA-Binding Proteins Membrane Proteins Nerve Tissue Proteins Peptide Fragments Phosphoproteins Proteins Tumor Suppressor Proteins ATM protein, human Ataxia Telangiectasia Mutated Proteins Atm protein, mouse Protein Serine-Threonine Kinases
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Lim D S
Oncology Center, The Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Kirsch D G
Canman C E
Ahn J H
Ziv Y
Newman L S
Darnell R B
Shiloh Y
Kastan M B
References (46)
46 references, click to expand
  1. A coat subunit of Golgi-derived non-clathrin-coated vesicles with homology to the clathrin-coated vesicle coat protein beta-adaptin.
    Nature. 1991 Jan 17;349(6306):215-20 PMID: 1898984
  2. Role of Drosophila alpha-adaptin in presynaptic vesicle recycling.
    Cell. 1997 Mar 21;88(6):767-76 PMID: 9118220
  3. Interaction of phosphoinositide cycle intermediates with the plasma membrane-associated clathrin assembly protein AP-2.
    J Biol Chem. 1991 Mar 5;266(7):4442-7 PMID: 1847920
  4. Inositol hexakisphosphate receptor identified as the clathrin assembly protein AP-2.
    Biochem Biophys Res Commun. 1992 Aug 31;187(1):158-63 PMID: 1325787
  5. A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia.
    Cell. 1992 Nov 13;71(4):587-97 PMID: 1423616
  6. The retinoblastoma protein associates with the protein phosphatase type 1 catalytic subunit.
    Genes Dev. 1993 Apr;7(4):555-69 PMID: 8384581
  7. Ionizing radiation and UV induction of p53 protein by different pathways in ataxia-telangiectasia cells.
    Oncogene. 1993 Dec;8(12):3307-12 PMID: 8247533
  8. The p53-dependent G1 cell cycle checkpoint pathway and ataxia-telangiectasia.
    Cancer Res. 1994 Oct 1;54(19):5054-8 PMID: 7923116
  9. The role of clathrin, adaptors and dynamin in endocytosis.
    Curr Opin Cell Biol. 1994 Aug;6(4):538-44 PMID: 7986531
  10. The appendage domain of alpha-adaptin is a high affinity binding site for dynamin.
    J Biol Chem. 1995 Apr 28;270(17):10079-83 PMID: 7730311
  11. A single ataxia telangiectasia gene with a product similar to PI-3 kinase.
    Science. 1995 Jun 23;268(5218):1749-53 PMID: 7792600
  12. Beta-NAP, a cerebellar degeneration antigen, is a neuron-specific vesicle coat protein.
    Cell. 1995 Sep 8;82(5):773-83 PMID: 7671305
  13. When is a lipid kinase not a lipid kinase? When it is a protein kinase.
    Cell. 1995 Oct 6;83(1):1-4 PMID: 7553860
  14. A role of amphiphysin in synaptic vesicle endocytosis suggested by its binding to dynamin in nerve terminals.
    Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):331-5 PMID: 8552632
  15. Regulation of RAD53 by the ATM-like kinases MEC1 and TEL1 in yeast cell cycle checkpoint pathways.
    Science. 1996 Jan 19;271(5247):357-60 PMID: 8553072
  16. The complete sequence of the coding region of the ATM gene reveals similarity to cell cycle regulators in different species.
    Hum Mol Genet. 1995 Nov;4(11):2025-32 PMID: 8589678
  17. Phosphoinositides as regulators in membrane traffic.
    Science. 1996 Mar 15;271(5255):1533-9 PMID: 8599109
  18. Interaction of Shc with adaptor protein adaptins.
    J Biol Chem. 1996 Mar 1;271(9):5265-9 PMID: 8617812
  19. The ear of alpha-adaptin interacts with the COOH-terminal domain of the Eps 15 protein.
    J Biol Chem. 1996 May 17;271(20):12111-6 PMID: 8662627
  20. Receptor signalling and the regulation of endocytic membrane transport.
    Curr Opin Cell Biol. 1996 Aug;8(4):549-56 PMID: 8791448
  21. Defective signaling through the B cell antigen receptor in Epstein-Barr virus-transformed ataxia-telangiectasia cells.
    J Biol Chem. 1997 Apr 4;272(14):9489-95 PMID: 9083089
  22. p53 and ATM: cell cycle, cell death, and cancer.
    Adv Cancer Res. 1997;71:1-25 PMID: 9111862
  23. The genetic defect in ataxia-telangiectasia.
    Annu Rev Immunol. 1997;15:177-202 PMID: 9143686
  24. Cellular localisation of the ataxia-telangiectasia (ATM) gene product and discrimination between mutated and normal forms.
    Oncogene. 1997 Apr 24;14(16):1911-21 PMID: 9150358
  25. Characterization of the adaptor-related protein complex, AP-3.
    J Cell Biol. 1997 May 19;137(4):835-45 PMID: 9151686
  26. Recombinant ATM protein complements the cellular A-T phenotype.
    Oncogene. 1997 Jul 10;15(2):159-67 PMID: 9244351
  27. Overexpression of a kinase-inactive ATR protein causes sensitivity to DNA-damaging agents and defects in cell cycle checkpoints.
    EMBO J. 1998 Jan 2;17(1):159-69 PMID: 9427750
  28. A function for the AP3 coat complex in synaptic vesicle formation from endosomes.
    Cell. 1998 May 1;93(3):423-32 PMID: 9590176
  29. Immunologic studies in ataxia-telangiectasia. I. Delayed hypersensitivity and serum immune globulin levels in probands and first-degree relatives.
    Int Arch Allergy Appl Immunol. 1966;30(1):15-29 PMID: 4161835
  30. Ataxia-telangiectasia. Electron microscopic study of a nerve biopsy.
    Bull Los Angeles Neurol Soc. 1969 Jan;34(1):23-38 PMID: 5764517
  31. Immunoglobulin E deficiency in ataxia-telangiectasia.
    N Engl J Med. 1969 Aug 28;281(9):469-72 PMID: 4183711
  32. [Ataxia teleangiectasia; electron microscopic study of two nerve biopsies].
    Z Neurol. 1972;202(2):128-38 PMID: 4115922
  33. Ataxia-telangiectasia (Louis Bar syndrome): with special reference to findings in the peripheral nervous system.
    Psychiatr Neurol Neurochir. 1973 Nov-Dec;76(6):459-72 PMID: 4150024
  34. Growth of cultured cells from patients with ataxia-telangiectasia.
    J Cell Physiol. 1976 NOV;89(3):429-31 PMID: 977661
  35. Extreme insulin resistance in ataxia telangiectasia: defect in affinity of insulin receptors.
    N Engl J Med. 1978 May 25;298(21):1164-71 PMID: 651946
  36. Mitogen receptor redistribution defects and concomitant absence of blastogenesis in ataxia-telangiectasia T lymphocytes.
    Clin Immunol Immunopathol. 1980 Jan;15(1):66-75 PMID: 6965620
  37. Colony-forming ability of ataxia-telangiectasia skin fibroblasts is an indicator of their early senescence and increased demand for growth factors.
    Exp Cell Res. 1982 Jul;140(1):191-9 PMID: 6213420
  38. Studies on lymphocyte cell surface in ataxia-telangiectasia.
    Clin Exp Immunol. 1985 Jul;61(1):118-24 PMID: 2994921
  39. Altered cellular morphology and microfilament array in ataxia-telangiectasia fibroblasts.
    Eur J Cell Biol. 1985 Nov;39(1):161-6 PMID: 3910438
  40. Lymphocyte gamma-glutamyltranspeptidase activity in ataxia-telangiectasia.
    Biochem Med Metab Biol. 1986 Dec;36(3):377-81 PMID: 2879550
  41. A versatile in vivo and in vitro eukaryotic expression vector for protein engineering.
    Nucleic Acids Res. 1988 Jan 11;16(1):369 PMID: 3340539
  42. Plasma membrane potential of lymphocytes from ataxia telangiectasia patients.
    Clin Biochem. 1989 Dec;22(6):469-73 PMID: 2611994
  43. The product of the ATM gene is a 370-kDa nuclear phosphoprotein.
    J Biol Chem. 1996 Dec 27;271(52):33693-7 PMID: 8969240
  44. Analysis of the ATM protein in wild-type and ataxia telangiectasia cells.
    Oncogene. 1996 Dec 19;13(12):2707-16 PMID: 9000145
  45. The ataxia-telangiectasia gene product, a constitutively expressed nuclear protein that is not up-regulated following genome damage.
    Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1840-5 PMID: 9050866
  46. Beta-COP, a 110 kd protein associated with non-clathrin-coated vesicles and the Golgi complex, shows homology to beta-adaptin.
    Cell. 1991 Feb 8;64(3):649-65 PMID: 1840503
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.17.10146
Published
1998-08-18
Pages
10146-51
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC21476
Subset
IM
Grants
NCI NIH HHS · R01 CA071387 · United States
NIGMS NIH HHS · T32 GM007309 · United States
NCI NIH HHS · CA71387 · United States
NIGMS NIH HHS · GM07309 · United States
External Links
PubMed source DOI: 10.1073/pnas.95.17.10146 PMC Full Text View journal details
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