Role of the cytoplasmic domain of the L1 cell adhesion molecule in brain development

Authors

  • Yukiko Nakamura,

    1. The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida 33136
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    • The first two authors contributed equally to this work.

  • Suni Lee,

    1. The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida 33136
    2. Department of Neuroscience, Case Western Reserve University, Cleveland, Ohio 44106
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    • The first two authors contributed equally to this work.

  • Candace L. Haddox,

    1. The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida 33136
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  • Eli J. Weaver,

    1. The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida 33136
    2. Department of Neuroscience, Case Western Reserve University, Cleveland, Ohio 44106
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  • Vance P. Lemmon

    Corresponding author
    1. The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida 33136
    2. Department of Neuroscience, Case Western Reserve University, Cleveland, Ohio 44106
    • The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Lois Pope LIFE Center (R48), 1095 NW 14th Terrace, Miami, FL 33136
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Abstract

Mutations in the human L1CAM gene cause X-linked hydrocephalus and MASA (Mental retardation, Aphasia, Shuffling gait, Adducted thumbs) syndrome. In vitro studies have shown that the L1 cytoplasmic domain (L1CD) is involved in L1 trafficking, neurite branching, signaling, and interactions with the cytoskeleton. L1cam knockout (L1KO) mice have hydrocephalus, a small cerebellum, hyperfasciculation of corticothalamic tracts, and abnormal peripheral nerves. To explore the function of the L1CD, we made three new mice lines in which different parts of the L1CD have been altered. In all mutant lines L1 protein is expressed and transported into the axon. Interestingly, these new L1CD mutant lines display normal brain morphology. However, the expression of L1 protein in the adult is dramatically reduced in the two L1CD mutant lines that lack the ankyrin-binding region and they show defects in motor function. Therefore, the L1CD is not responsible for the major defects observed in L1KO mice, yet it is required for continued L1 protein expression and motor function in the adult. J. Comp. Neurol. 518:1113–1132, 2010. © 2009 Wiley-Liss, Inc.

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