The cerebellar leucine-rich acidic nuclear protein interacts with ataxin-1 (original) (raw)

Nature volume 389, pages 974–978 (1997)Cite this article

A Corrigendum to this article was published on 19 February 1998

Abstract

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder characterized by ataxia, progressive motor deterioration, and loss of cerebellar Purkinje cells1. SCA1 belongs to a growing group of neurodegenerative disorders caused by expansion of CAG repeats, which encode glutamine2. Although the proteins containing these repeats are widely expressed, the neurodegeneration in SCA1 and other polyglutamine diseases selectively involves a few neuronal subtypes. The mechanism(s) underlying this neuronal specificity is unknown. Here we show that the cerebellar leucine-rich acidic nuclear protein (LANP)3 interacts with ataxin-1, the SCA1 gene product. LANP is expressed predominantly in Purkinje cells, the primary site of pathology in SCA1. The interaction between LANP and ataxin-1 is significantly stronger when the number of glutamines is increased. Immunofluorescence studies demonstrate that both LANP and ataxin-1 colocalize in nuclear matrix-associated subnuclear structures. The features of the interaction between ataxin-1 and LANP, their spatial and temporal patterns of expression, and the colocalization studies indicate that cerebellar LANP is involved in the pathogenesis of SCA1.

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Acknowledgements

We thank S. Elledge for the Y187 and Y190 yeast strains, pAS2-CYH2 and pACT2 vectors, and constructs expressing Lamin, SNF1, Tat, Cdc25, p53, Rb, Rev, cyclin D1, Cdk2 and Cdk6; E. N. Olson for the mouse brain cDNA library; D. Beach for the Hf7c yeast strain; D. Armstrong for neuropathological expertise; S. Y. Tsai for the expression vector containing SP1; R. C. Atkinson for assistance with confocal microscopy; R. Phillips and B. Antalffy for technical expertise; and A. Beaudet for critically reading the manuscript. This work was supported by grants from the NIH to H.Y.Z. and H.T.O. and by the Baylor College of Medicne Mental Retardation Research Center. A.M. was supported by a postdoctoral fellowship from the Spanish Ministerio de Educación y Ciencia.

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  1. Huda Y. Zoghbi: Correspondence and requests for materials should be addressed to H.Y.Z.

Authors and Affiliations

  1. Departments of Pediatrics, Houston, 77030, Texas, USA
    Antoni Matilla, Beena T. Koshy, Christopher J. Cummings & Huda Y. Zoghbi
  2. Departments of Molecular and Human Genetics, and Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, 77030, Texas, USA
    Christopher J. Cummings & Huda Y. Zoghbi
  3. Departments of Howard Hughes Medical Institute, Houston, 77030, Texas, USA
    Huda Y. Zoghbi
  4. Department of Chemistry, Faculty of Science, Tokyo Metropolitan University, Tokyo, Japan
    Toshiaki Isobe
  5. Departments of Laboratory Medicine and Pathology, and Biochemistry, and Institute of Human Genetics, University of Minnesota, Minneapolis, 55455, Minnesota, USA
    Harry T. Orr

Authors

  1. Antoni Matilla
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  2. Beena T. Koshy
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  3. Christopher J. Cummings
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  4. Toshiaki Isobe
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  5. Harry T. Orr
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  6. Huda Y. Zoghbi
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Correspondence toHuda Y. Zoghbi.

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Matilla, A., Koshy, B., Cummings, C. et al. The cerebellar leucine-rich acidic nuclear protein interacts with ataxin-1.Nature 389, 974–978 (1997). https://doi.org/10.1038/40159

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