Activated leukocyte cell adhesion molecule modulates neurotrophin signaling
Article first published online: 10 FEB 2012
© 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry
Journal of Neurochemistry
Volume 121, Issue 4, pages 575–586, May 2012
How to Cite
Wade, A., Thomas, C., Kalmar, B., Terenzio, M., Garin, J., Greensmith, L. and Schiavo, G. (2012), Activated leukocyte cell adhesion molecule modulates neurotrophin signaling. Journal of Neurochemistry, 121: 575–586. doi: 10.1111/j.1471-4159.2012.07658.x
- Issue published online: 12 APR 2012
- Article first published online: 10 FEB 2012
- Accepted manuscript online: 13 JAN 2012 02:14PM EST
- Received October 31, 2011; revised manuscript received December 17, 2011, accepted January 10, 2012.
- axonal transport;
- motor neuron;
- neurite outgrowth;
- neurotrophin receptor;
- signaling endosome
J. Neurochem. (2012) 121, 575–586.
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.