Integrin α9β1 is a receptor for nerve growth factor and other neurotrophins

The integrin α9β1 is a multifunctional receptor that interacts with a variety of ligands including vascular cell adhesion molecule 1, tenascin C and osteopontin. We found that this integrin is a receptor for nerve growth factor (NGF) and two other neurotrophins, brain-derived neurotrophic factor and NT3, using a cell adhesion assay with the α9SW480 cell line. Interaction of α9β1 with NGF was confirmed in an ELISA assay by direct binding to purified integrin. α9β1 integrin binds to neurotrophins in a manner similar to another common neurotrophin receptor, p75NTR (NGFR), although α9β1 activity is correlated with induction of pro-survival and pro-proliferative signaling cascades. This property of α9β1 resembles the interaction of NGF with a high affinity receptor, TrkA, however, this integrin shows a low affinity for NGF. NGF induces chemotaxis of cells expressing α9β1 and their proliferation. Moreover, α9β1 integrin is a signaling receptor for NGF, which activates the MAPK (Erk1/2) pathway. The α9β1-dependent chemotactic ability of NGF appears to result from the activation of paxillin.