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beta1-integrin mediates myelin-associated glycoprotein signaling in neuronal growth cones |
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| Authors: | Eyleen LK Goh Ju Kim Young Kenichiro Kuwako Marc Tessier-Lavigne Zhigang He John W Griffin Guo-li Ming |
| Affiliation: | 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 |
| 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. |
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