Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

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

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Polydom/SVEP1 Is a Ligand for Integrin {alpha}9{beta}1.
R. Sato-Nishiuchi, I. Nakano, A. Ozawa, Y. Sato, M. Takeichi, D. Kiyozumi, K. Yamazaki, T. Yasunaga, S. Futaki, and K. Sekiguchi (2012)
J. Biol. Chem. 287, 25615-25630
   Abstract »    Full Text »    PDF »
Importance of interaction between nerve growth factor and {alpha}9{beta}1 integrin in glial tumor angiogenesis.
E. M. Walsh, R. Kim, L. Del Valle, M. Weaver, J. Sheffield, P. Lazarovici, and C. Marcinkiewicz (2012)
Neuro Oncology 14, 890-901
   Abstract »    Full Text »    PDF »
Matrix Metalloproteinase-9 Regulates Survival of Neurons in Newborn Hippocampus.
S. Murase and R. D. McKay (2012)
J. Biol. Chem. 287, 12184-12194
   Abstract »    Full Text »    PDF »
In the Newborn Hippocampus, Neurotrophin-Dependent Survival Requires Spontaneous Activity and Integrin Signaling.
S. Murase, D. F. Owens, and R. D. McKay (2011)
J. Neurosci. 31, 7791-7800
   Abstract »    Full Text »    PDF »
Vascular Endothelial Growth Factor A (VEGF-A) Induces Endothelial and Cancer Cell Migration through Direct Binding to Integrin {alpha}9{beta}1: IDENTIFICATION OF A SPECIFIC {alpha}9{beta}1 BINDING SITE.
S. Oommen, S. K. Gupta, and N. E. Vlahakis (2011)
J. Biol. Chem. 286, 1083-1092
   Abstract »    Full Text »    PDF »
Integrin {alpha}9{beta}1 mediates enhanced cell migration through nitric oxide synthase activity regulated by Src tyrosine kinase.
S. K. Gupta and N. E. Vlahakis (2009)
J. Cell Sci. 122, 2043-2054
   Abstract »    Full Text »    PDF »
{alpha}9 Integrin Promotes Neurite Outgrowth on Tenascin-C and Enhances Sensory Axon Regeneration.
M. R. Andrews, S. Czvitkovich, E. Dassie, C. F. Vogelaar, A. Faissner, B. Blits, F. H. Gage, C. ffrench-Constant, and J. W. Fawcett (2009)
J. Neurosci. 29, 5546-5557
   Abstract »    Full Text »    PDF »
Regulatory effect of nerve growth factor in {alpha}9{beta}1 integrin-dependent progression of glioblastoma.
M. C. Brown, I. Staniszewska, P. Lazarovici, G. P. Tuszynski, L. Del Valle, and C. Marcinkiewicz (2008)
Neuro Oncology 10, 968-980
   Abstract »    Full Text »    PDF »
The integrin {alpha}9{beta} 1 is a receptor for nerve growth factor and other neurotrophins.
I. Staniszewska, I. K. Sariyer, S. Lecht, M. C. Brown, E. M. Walsh, G. P. Tuszynski, M. Safak, P. Lazarovici, and C. Marcinkiewicz (2008)
Development 135, e1
   Full Text »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882