CLN3, the protein associated with batten disease: Structure, function and localization

Authors

  • Seasson N. Phillips,

    1. Center for Aging and Developmental Biology, University of Rochester School of Medicine and Dentistry, Rochester, New York
    2. Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York
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  • Jared W. Benedict,

    1. Center for Aging and Developmental Biology, University of Rochester School of Medicine and Dentistry, Rochester, New York
    2. Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York
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  • Jill M. Weimer,

    1. Center for Aging and Developmental Biology, University of Rochester School of Medicine and Dentistry, Rochester, New York
    2. Interdepartment Program in Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, New York
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  • David A. Pearce

    Corresponding author
    1. Center for Aging and Developmental Biology, University of Rochester School of Medicine and Dentistry, Rochester, New York
    2. Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York
    3. Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, New York
    • Center for Aging and Developmental Biology, Box 645, University of Rochester School of Medicine and Dentistry, Rochester NY 14642
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Abstract

Batten disease, an inherited neurodegenerative storage disease affecting children, results from the autosomal recessive inheritance of mutations in Cln3. The function of the CLN3 protein remains unknown. A key to understanding the pathology of this devastating disease will be to elucidate the function of CLN3 at the cellular level. CLN3 has proven difficult to study as it is predicted to be a membrane protein expressed at relatively low levels. This article is a critical review of various approaches used in examining the structure, trafficking, and localization of CLN3. We conclude that CLN3 is likely resident in the lysosomal/endosomal membrane. Different groups have postulated conflicting orientations for CLN3 within this membrane. In addition, CLN3 undergoes several posttranslational modifications and is trafficked through the endoplasmic reticulum and Golgi. Recent evidence also suggests that CLN3 traffics via the plasma membrane. Although the function of this protein remains elusive, it is apparent that genetic alterations in Cln3 may have a direct affect on lysosomal function. © 2005 Wiley-Liss, Inc.

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