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Integrin activation and neurotrophin signaling cooperate to enhance neurite outgrowth in sensory neurons
Author(s) -
Tucker Budd A.,
Rahimtula Masuma,
Mearow Karen M.
Publication year - 2005
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.20518
Subject(s) - neurite , nerve growth factor , microbiology and biotechnology , integrin , biology , dorsal root ganglion , neurotrophin , proto oncogene tyrosine protein kinase src , signal transduction , integrin alpha m , neurotrophin 3 , laminin , neuroscience , neurotrophic factors , extracellular matrix , receptor , brain derived neurotrophic factor , biochemistry , sensory system , in vitro
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 β1‐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 β1‐integrin blocking antibody, β1i, 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. J. Comp. Neurol. 486:267–280, 2005. © 2005 Wiley‐Liss, Inc.