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Activated leukocyte cell adhesion molecule modulates neurotrophin signaling
Author(s) -
Wade Anna,
Thomas Claire,
Kalmar Bernadett,
Terenzio Marco,
Garin Jerome,
Greensmith Linda,
Schiavo Giampietro
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2012.07658.x
Subject(s) - alcam , neurotrophin , microbiology and biotechnology , neurite , nerve growth factor , immunoglobulin superfamily , neural cell adhesion molecule , cell adhesion molecule , growth cone , biology , neurotrophic factors , axon , neuroscience , signal transduction , cell adhesion , axoplasmic transport , receptor , cell , biochemistry , in vitro
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 p75 NTR 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.