Integrin activation and neurotrophin signaling cooperate to enhance neurite outgrowth in sensory neurons

Abstract

Neurite growth is influenced by many factors, including the availability of trophic support as well as the extracellular environment. In this study, we have investigated whether attachment to a permissive culture substrate such as laminin is sufficient to promote neurite outgrowth from dorsal root ganglion neurons in the absence of added nerve growth factor (NGF) and whether this attachment can enhance the response of these neurons to NGF. Adult dorsal root ganglia neurons plated on surfaces coated with a thin film of laminin exhibited increased neurite outgrowth. This effect was integrin-dependent as it was attenuated by treatment with RGD (arginine-glycine-aspartate) peptides and by a beta1-integrin blocking antibody. The addition of NGF resulted in a significant increase in the integrin-dependent outgrowth. We have correlated this increase in growth with increased expression of integrin subunits and activation of known downstream signaling intermediates such as focal adhesion kinase, Src, and Akt. We have also examined pathway cooperation through the use of an Src-specific inhibitor, PP2, and a beta1-integrin blocking antibody, beta1i, by observing downstream signaling intermediates in both integrin and growth factor signaling pathways. These results are among the first to detail the importance of interactions between neurotrophin- and integrin-activated signaling in adult primary neurons.

Brain-Derived Neurotrophic Factor Promotes Long-Term Potentiation-Related Cytoskeletal Changes in Adult Hippocampus

“…Interactions between integrin and trophic factor receptor signaling cascades are commonplace (Fu et al, 2001;Miranti and Brugge, 2002;Yamada and Even-Ram, 2002), and many trophic functions are now understood to require, or to be enhanced by, the engagement of both classes of receptors (ffrench-Constant and Colognato, 2004;Tucker et al, 2005). It is thus reasonable to anticipate that integrin-and BDNF-mediated signaling cascades set in motion by theta stimulation converge on downstream elements regulating actin polymerization.…”

Targeting Axon Growth from Neuronal Transplants along Preformed Guidance Pathways in the Adult CNS

“…The combination of NGF availability and the highly vascular nature of the leptomeninges may have led to this pathway decision, because endothelial basement membranes are a rich source of laminin. Laminin, by way of integrin receptors, activates signaling pathways that overlap downstream with NGF signaling pathways, leading to further enhanced neurite outgrowth from sensory neurons (Liu et al, 2002;Tucker et al, 2005). In addition, these axons follow a path of least resistance (Ramon y Cajal, 1928), in which there are less growth constraints for axons growing within the relative openness of the subarachnoid space than within the densely myelinated corpus callosum.…”

Intracerebral Peripheral Blood Stem Cell (CD34+) Implantation Induces Neuroplasticity by Enhancing β1 Integrin-Mediated Angiogenesis in Chronic Stroke Rats

“…Finally, in this study, angiogenic growth factors such as SDF-1 and VEGF were significantly upregulated in PBSC-treated rats compared with controltreated rats. Therefore, angiogenic growth factor and some adhesion molecules produced by an interaction between implanted stem cells and host brain parenchymal cells might initiate MA/MI adherence to sites of occluded vessels (Buschmann et al, 2003;Pipp et al, 2003;Shastry and Tyagi, 2004;Li et al, 2005;Tucker et al, 2005). Subsequently, MA/MI began to release some proteinases to guide vascular remodeling in the ischemic brain (Fujiyama et al, 2003;Milner and Campbell, 2003;Pipp et al, 2003).…”