Home LiteratureArticle Details
PMID: 8760814 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Selective loss of sarcolemmal nitric oxide synthase in Becker muscular dystrophy.

The Journal of experimental medicine ·Vol. 184 ·No. 2 ·1996-08-01 ·Pages 609-18

Chao DS, Gorospe JR, Brenman JE, Rafael JA, Peters MF, Froehner SC, Hoffman EP, Chamberlain JS, Bredt DS

Abstract

Becker muscular dystrophy is an X-linked disease due to mutations of the dystrophin gene. We now show that neuronal-type nitric oxide synthase (nNOS), an identified enzyme in the dystrophin complex, is uniquely absent from skeletal muscle plasma membrane in many human Becker patients and in mouse models of dystrophinopathy. An NH2-terminal domain of nNOS directly interacts with alpha 1-syntrophin but not with other proteins in the dystrophin complex analyzed. However, nNOS does not associate with alpha 1-syntrophin on the sarcolemma in transgenic mdx mice expressing truncated dystrophin proteins. This suggests a ternary interaction of nNOS, alpha 1-syntrophin, and the central domain of dystrophin in vivo, a conclusion supported by developmental studies in muscle. These data indicate that proper assembly of the dystrophin complex is dependent upon the structure of the central rodlike domain and have implications for the design of dystrophin-containing vectors for gene therapy.

MeSH Terms
Animals Biopsy Calcium-Binding Proteins Cytoskeletal Proteins/metabolism Fluorescent Antibody Technique, Indirect Humans Membrane Glycoproteins/metabolism Membrane Proteins/metabolism Mice Mice, Mutant Strains Muscle Proteins/metabolism Muscles/metabolism Muscular Dystrophies/enzymology Nitric Oxide Synthase/metabolism Sarcoglycans Sarcolemma/enzymology Utrophin
Chemicals
Calcium-Binding Proteins Cytoskeletal Proteins Membrane Glycoproteins Membrane Proteins Muscle Proteins Sarcoglycans Utrn protein, mouse Utrophin syntrophin alpha1 Nitric Oxide Synthase
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Chao D S
Department of Physiology, University of California at San Francisco School of Medicine 94143-0444, USA.
Gorospe J R
Brenman J E
Rafael J A
Peters M F
Froehner S C
Hoffman E P
Chamberlain J S
Bredt D S
References (40)
40 references, click to expand
  1. Syntrophin binds to an alternatively spliced exon of dystrophin.
    J Cell Biol. 1995 Feb;128(3):363-71 PMID: 7844150
  2. Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha1-syntrophin mediated by PDZ domains.
    Cell. 1996 Mar 8;84(5):757-67 PMID: 8625413
  3. The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein.
    Cell. 1988 Apr 22;53(2):219-28 PMID: 3282674
  4. Characterization of dystrophin in muscle-biopsy specimens from patients with Duchenne's or Becker's muscular dystrophy.
    N Engl J Med. 1988 May 26;318(21):1363-8 PMID: 3285207
  5. Improved diagnosis of Becker muscular dystrophy by dystrophin testing.
    Neurology. 1989 Aug;39(8):1011-7 PMID: 2668783
  6. Dystrophin diagnosis: comparison of dystrophin abnormalities by immunofluorescence and immunoblot analyses.
    Proc Natl Acad Sci U S A. 1989 Sep;86(18):7154-8 PMID: 2674948
  7. Deficiency of a glycoprotein component of the dystrophin complex in dystrophic muscle.
    Nature. 1990 May 24;345(6273):315-9 PMID: 2188135
  8. Localization of nitric oxide synthase indicating a neural role for nitric oxide.
    Nature. 1990 Oct 25;347(6295):768-70 PMID: 1700301
  9. Somatic reversion/suppression of the mouse mdx phenotype in vivo.
    J Neurol Sci. 1990 Oct;99(1):9-25 PMID: 2250176
  10. Purification of dystrophin from skeletal muscle.
    J Biol Chem. 1991 May 15;266(14):9161-5 PMID: 2026615
  11. Exploring the molecular basis for variability among patients with Becker muscular dystrophy: dystrophin gene and protein studies.
    Am J Hum Genet. 1991 Jul;49(1):54-67 PMID: 2063877
  12. Primary structure of dystrophin-associated glycoproteins linking dystrophin to the extracellular matrix.
    Nature. 1992 Feb 20;355(6362):696-702 PMID: 1741056
  13. Expression of the N-terminal domain of dystrophin in E. coli and demonstration of binding to F-actin.
    FEBS Lett. 1992 Apr 27;301(3):243-5 PMID: 1577159
  14. Dystrophin and the membrane skeleton.
    Curr Opin Cell Biol. 1993 Feb;5(1):82-7 PMID: 8448034
  15. Overexpression of dystrophin in transgenic mdx mice eliminates dystrophic symptoms without toxicity.
    Nature. 1993 Aug 19;364(6439):725-9 PMID: 8355788
  16. Two forms of mouse syntrophin, a 58 kd dystrophin-associated protein, differ in primary structure and tissue distribution.
    Neuron. 1993 Sep;11(3):531-40 PMID: 7691103
  17. Genotype/phenotype correlations in Duchenne/Becker dystrophy.
    Mol Cell Biol Hum Dis Ser. 1993;3:12-36 PMID: 8111537
  18. Heterogeneity of the 59-kDa dystrophin-associated protein revealed by cDNA cloning and expression.
    J Biol Chem. 1994 Feb 25;269(8):6040-4 PMID: 8119949
  19. Molecular organization at the glycoprotein-complex-binding site of dystrophin. Three dystrophin-associated proteins bind directly to the carboxy-terminal portion of dystrophin.
    Eur J Biochem. 1994 Mar 1;220(2):283-92 PMID: 8125086
  20. Nitric oxide as a messenger molecule for myoblast fusion.
    J Biol Chem. 1994 May 20;269(20):14371-4 PMID: 7514168
  21. A role for dystrophin-associated glycoproteins and utrophin in agrin-induced AChR clustering.
    Cell. 1994 Jun 3;77(5):663-74 PMID: 8205616
  22. Dystroglycan-alpha, a dystrophin-associated glycoprotein, is a functional agrin receptor.
    Cell. 1994 Jun 3;77(5):675-86 PMID: 8205617
  23. Missense mutations in the adhalin gene linked to autosomal recessive muscular dystrophy.
    Cell. 1994 Aug 26;78(4):625-33 PMID: 8069911
  24. Nitric oxide in skeletal muscle.
    Nature. 1994 Dec 8;372(6506):546-8 PMID: 7527495
  25. beta 2-Syntrophin: localization at the neuromuscular junction in skeletal muscle.
    Neuroreport. 1994 Aug 15;5(13):1577-80 PMID: 7819523
  26. Prevention of dystrophic pathology in mdx mice by a truncated dystrophin isoform.
    Hum Mol Genet. 1994 Oct;3(10):1725-33 PMID: 7849695
  27. Nitric oxide mediates activity-dependent synaptic suppression at developing neuromuscular synapses.
    Nature. 1995 Mar 16;374(6519):262-6 PMID: 7885445
  28. Identification of alpha-syntrophin binding to syntrophin triplet, dystrophin, and utrophin.
    J Biol Chem. 1995 Mar 10;270(10):4975-8 PMID: 7890602
  29. Dp71 can restore the dystrophin-associated glycoprotein complex in muscle but fails to prevent dystrophy.
    Nat Genet. 1994 Dec;8(4):333-9 PMID: 7894482
  30. Exogenous Dp71 restores the levels of dystrophin associated proteins but does not alleviate muscle damage in mdx mice.
    Nat Genet. 1994 Dec;8(4):340-4 PMID: 7894483
  31. G beta gamma interactions with PH domains and Ras-MAPK signaling pathways.
    Trends Biochem Sci. 1995 Apr;20(4):151-6 PMID: 7770915
  32. Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy.
    Cell. 1995 Sep 8;82(5):743-52 PMID: 7545544
  33. Species-independent expression of nitric oxide synthase in the sarcolemma region of visceral and somatic striated muscle fibers.
    Cell Tissue Res. 1995 Sep;281(3):493-9 PMID: 7553769
  34. Mouse alpha 1- and beta 2-syntrophin gene structure, chromosome localization, and homology with a discs large domain.
    J Biol Chem. 1995 Oct 27;270(43):25859-65 PMID: 7592771
  35. Beta-sarcoglycan: characterization and role in limb-girdle muscular dystrophy linked to 4q12.
    Nat Genet. 1995 Nov;11(3):257-65 PMID: 7581448
  36. Beta-sarcoglycan (A3b) mutations cause autosomal recessive muscular dystrophy with loss of the sarcoglycan complex.
    Nat Genet. 1995 Nov;11(3):266-73 PMID: 7581449
  37. Mutations in the dystrophin-associated protein gamma-sarcoglycan in chromosome 13 muscular dystrophy.
    Science. 1995 Nov 3;270(5237):819-22 PMID: 7481775
  38. Expression of human full-length and minidystrophin in transgenic mdx mice: implications for gene therapy of Duchenne muscular dystrophy.
    Hum Mol Genet. 1995 Aug;4(8):1245-50 PMID: 7581360
  39. Expression of full-length and truncated dystrophin mini-genes in transgenic mdx mice.
    Hum Mol Genet. 1995 Aug;4(8):1251-8 PMID: 7581361
  40. Mammalian alpha 1- and beta 1-syntrophin bind to the alternative splice-prone region of the dystrophin COOH terminus.
    J Cell Biol. 1995 Feb;128(3):373-81 PMID: 7844151
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.184.2.609
Published
1996-08-01
Pages
609-18
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2192729
Subset
IM
Grants
NINDS NIH HHS · R0INS34822 · United States
External Links
PubMed source DOI: 10.1084/jem.184.2.609 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2