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J. Cell Sci. 121 (4): 504-513


Research Article

Integrin {alpha}9β1 is a receptor for nerve growth factor and other neurotrophins

Izabela Staniszewska1, Ilker K. Sariyer1, Shimon Lecht2, Meghan C. Brown1, Erin M. Walsh1, George P. Tuszynski1, Mahmut Safak1, Philip Lazarovici2, and Cezary Marcinkiewicz1,*

1 Department of Neuroscience, Center for Neurovirology and Cancer Biology, Temple University, School of Medicine, Philadelphia, PA 19122, USA
2 Department of Pharmacology and Experimental Therapeutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, School of Pharmacy, Jerusalem 91120, Israel

* Author for correspondence (e-mail: cmarcink{at}temple.edu)

Accepted for publication 8 November 2007.

Abstract: The integrin {alpha}9β1 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}9β1 with NGF was confirmed in an ELISA assay by direct binding to purified integrin. {alpha}9β1 integrin binds to neurotrophins in a manner similar to another common neurotrophin receptor, p75NTR (NGFR), although {alpha}9β1 activity is correlated with induction of pro-survival and pro-proliferative signaling cascades. This property of {alpha}9β1 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}9β1 and their proliferation. Moreover, {alpha}9β1 integrin is a signaling receptor for NGF, which activates the MAPK (Erk1/2) pathway. The {alpha}9β1-dependent chemotactic ability of NGF appears to result from the activation of paxillin.

Key Words: Integrins • Neurotrophins • Nerve growth factor • Cell adhesion • Proliferation • Migration


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