Activated leukocyte cell adhesion molecule modulates neurotrophin signaling

Authors

  • Anna Wade,

    1. Molecular NeuroPathobiology Laboratory, Cancer Research UK London Research Institute, London, UK
    2. Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, Queen Square, London, UK
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  • Claire Thomas,

    1. Molecular NeuroPathobiology Laboratory, Cancer Research UK London Research Institute, London, UK
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  • Bernadett Kalmar,

    1. Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, Queen Square, London, UK
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  • Marco Terenzio,

    1. Molecular NeuroPathobiology Laboratory, Cancer Research UK London Research Institute, London, UK
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  • Jerome Garin,

    1. CEA, IRTSV, Biologie à Grande Echelle, Grenoble, France
    2. INSERM, U1038, Grenoble, France
    3. Université Joseph Fourier, Grenoble 1, France
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  • Linda Greensmith,

    1. Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, Queen Square, London, UK
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  • Giampietro Schiavo

    1. Molecular NeuroPathobiology Laboratory, Cancer Research UK London Research Institute, London, UK
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Address correspondence and reprint requests to Giampietro Schiavo, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, WC2A 3LY London, UK. E-mail: giampietro.schiavo@cancer.org.uk

Abstract

J. Neurochem. (2012) 121, 575–586.

Abstract

Cell adhesion molecules of the immunoglobulin superfamily (IgCAMs) have been shown to modulate growth factor signaling and follow complex trafficking pathways in neurons. Similarly, several growth factors, including members of the neurotrophin family, undergo axonal retrograde transport that is required to elicit their full signaling potential in neurons. We sought to determine whether IgCAMs that enter the axonal retrograde transport route co-operate with neurotrophin signaling. We identified activated leukocyte cell adhesion molecule (ALCAM), a protein involved in axon pathfinding and development of the neuromuscular junction, to be associated with an axonal endocytic compartment that contains neurotrophins and their receptors. Although ALCAM enters carriers that are transported bidirectionally in motor neuron axons, it is predominantly co-transported with the neurotrophin receptor p75NTR toward the cell body. ALCAM was found to specifically potentiate nerve growth factor (NGF)-induced differentiation and signaling. The extracellular domain of ALCAM is both necessary and sufficient to potentiate NGF-induced neurite outgrowth, and its homodimerization is required for this novel role. Our findings indicate that ALCAM synergizes with NGF to induce neuronal differentiation, raising the possibility that it functions not only as an adhesion molecule but also in the modulation of growth factor signaling in the nervous system.

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