Research

beta1-integrin mediates myelin-associated glycoprotein signaling in neuronal growth cones

Eyleen LK Goh^1,2* , Ju Kim Young^1,2* , Kenichiro Kuwako³ , Marc Tessier-Lavigne⁴ , Zhigang He³ , John W Griffin^2,5 and Guo-li Ming^1,2,5

¹  Institute for Cell Engineering, The Johns Hopkins University School of Medicine, MD 21205, USA

²  Department of Neurology, The Johns Hopkins University School of Medicine, MD 21205, USA

³  Division of Neuroscience, Children's Hospital, Boston, MA 02115, USA

⁴  Division of Research, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA

⁵  The Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, MD 21205, USA

author email corresponding author email* Contributed equally

Molecular Brain 2008, 1:10doi:10.1186/1756-6606-1-10

Published:	15 October 2008

Abstract

Several myelin-associated factors that inhibit axon growth of mature neurons, including Nogo66, myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein (OMgp), can associate with a common GPI-linked protein Nogo-66 receptor (NgR). Accumulating evidence suggests that myelin inhibitors also signal through unknown NgR-independent mechanisms. Here we show that MAG, a RGD tri-peptide containing protein, forms a complex with β1-integrin to mediate axonal growth cone turning responses of several neuronal types. Mutations that alter the RGD motif in MAG or inhibition of β1-integrin function, but not removal of NgRs, abolish these MAG-dependent events. In contrast, OMgp-induced repulsion is not affected by inhibition of b1-integrin function. We further show that MAG stimulates tyrosine phosphorylation of focal adhesion kinase (FAK), which in turn is required for MAG-induced growth cone turning. These studies identify β1-integrin as a specific mediator for MAG in growth cone turning responses, acting through FAK activation.