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Letters to Nature

Nature 389, 974-978 (30 October 1997) | doi:10.1038/40159; Received 9 July 1997; Accepted 8 September 1997

The cerebellar leucine-rich acidic nuclear protein interacts with ataxin-1

Antoni Matilla1, Beena T. Koshy1, Christopher J. Cummings1,2, Toshiaki Isobe3, Harry T. Orr4 & Huda Y. Zoghbi1,2,5

  1. Departments of Pediatrics, Houston, Texas 77030, USA
  2. Departments of Molecular and Human Genetics, and Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
  3. Departments of Howard Hughes Medical Institute, Houston, Texas 77030, USA
  4. Department of Chemistry, Faculty of Science, Tokyo Metropolitan University, Tokyo, Japan
  5. Departments of Laboratory Medicine and Pathology, and Biochemistry, and Institute of Human Genetics, University of Minnesota, Minneapolis, Minnesota 55455, USA

Correspondence to: Correspondence and requests for materials should be addressed to H.Y.Z. (e-mail: Email: hzoghbi@bcm.tmc.edu).

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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.