Integrin alpha4beta1 (VLA-4) expression and activity in retinal and peripheral neurons

TitleIntegrin alpha4beta1 (VLA-4) expression and activity in retinal and peripheral neurons
Publication TypeJournal Article
Year of Publication2003
AuthorsHikita ST, Cann GM, Wingerd KL, Mullick LH, Wayne WC, Webb SW, Clegg DO
JournalMolecular and Cellular Neuroscience
Date Published2003 Jul
KeywordsAnimals, Chick Embryo, Epithelial Cells, Female, Ganglia, Spinal, Gene Expression Regulation, Developmental, Integrin alpha4beta1, Mice, Mice, Inbred C3H, Mice, Inbred C57BL, Neurites, Neurons, Pregnancy, Recombinant Proteins, Retinal Ganglion Cells, Solubility, Superior Cervical Ganglion, Vascular Cell Adhesion Molecule-1

The integrin alpha4beta1 fulfills important roles in inflammation and hematopoesis, but its functions in neurons are not well understood. Here we show that the alpha4 subunit is expressed on mouse retinal ganglion cells (RGCs) and undifferentiated retinal neuroblasts during the period of axon extension and migration. To determine if alpha4 integrins expressed by retinal neurons were active, neurons were cultured on known alpha4 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 alpha4. Neurite outgrowth on OPN was also blocked by antibodies to the integrin beta1 subunit, implicating the alpha4beta1 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 alpha4 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 alpha4beta1 may play a role in the development of multiple neuronal cell types.

Alternate JournalMol. Cell. Neurosci.
PubMed ID12837626
Grant ListEY09736 / EY / NEI NIH HHS / United States