Integrin α4β1 (VLA-4) expression and activity in retinal and peripheral neurons

Abstract The integrin α4β1 fulfills important roles in inflammation and hematopoesis, but its functions in neurons are not well understood. Here we show that the α4 subunit is expressed on mouse retinal ganglion cells (RGCs) and undifferentiated retinal neuroblasts during the period of axon extension and migration. To determine if α4 integrins expressed by retinal neurons were active, neurons were cultured on known α4 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 α4. Neurite outgrowth on OPN was also blocked by antibodies to the integrin β1 subunit, implicating the α4β1 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 α4 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 α4β1 may play a role in the development of multiple neuronal cell types.