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JCS ePress online publication date 29 Jan 2008
doi: 10.1242/jcs.000232

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Research Article

Integrin {alpha}9{beta}1 is a receptor for nerve growth factor and other neurotrophins


Izabela Staniszewska, Ilker K. Sariyer, Shimon Lecht, Meghan C. Brown, Erin M. Walsh, George P. Tuszynski, Mahmut Safak, Philip Lazarovici, and Cezary Marcinkiewicz*
* Author for correspondence (e-mail: cmarcink{at}temple.edu)

The integrin {alpha}9{beta}1 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 {alpha}9SW480 cell line. Interaction of {alpha}9{beta}1 with NGF was confirmed in an ELISA assay by direct binding to purified integrin. {alpha}9{beta}1 integrin binds to neurotrophins in a manner similar to another common neurotrophin receptor, p75NTR (NGFR), although {alpha}9{beta}1 activity is correlated with induction of pro-survival and pro-proliferative signaling cascades. This property of {alpha}9{beta}1 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 {alpha}9{beta}1 and their proliferation. Moreover, {alpha}9{beta}1 integrin is a signaling receptor for NGF, which activates the MAPK (Erk1/2) pathway. The {alpha}9{beta}1-dependent chemotactic ability of NGF appears to result from the activation of paxillin.


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