Integrin alpha 4 beta 1 (VLA-4) expression and activity in retinal and peripheral neurons

The integrin alpha 4 beta 1 fulfills important roles in inflammation and hematopoesis, but its functions in neurons are not well understood. Here we show that the alpha 4 subunit is expressed on mouse retinal ganglion cells (RGCs) and undifferentiated retinal neuroblasts during the period of axon extension and migration. To determine if alpha 4 integrins expressed by retinal neurons were active, neurons were cultured on known alpha 4 ligands in vitro. Recombinant soluble vascular cell adhesion molecule 1 (rsVCAM-1), fibronectin, and osteopontin (OPN) induced neurite outgrowth that was diminished by function blocking antibodies specific for alpha 4. Neurite outgrowth on OPN was also blocked by antibodies to the integrin beta 1 subunit, implicating the alpha 4 beta 1 heterodimer as one integrin receptor mediating outgrowth on OPN. OPN immunoreactivity was detected in the RGC fiber layer and optic nerve, suggesting that it may act as an alpha 4 ligand in vivo. Neurons from chick lumbar sympathetic ganglia, chick dorsal root ganglia, and mouse superior cervical ganglia also extended neurites on rsVCAM-1, suggesting that integrin alpha 4 beta 1 may play a role in the development of multiple neuronal cell types.