John van Geest Centre for Brain Repair

School of Clinical Medicine



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Integrins and the cell surface in axon regeneration

Cell process interact with the surrounding extracellular matrix mostly through integrins. Axons need to have the right integrin in order to regenerate in the damaged CNS, they need to have on their surface integrins that can interact with the matrix glycoproteins found there. Alpha9 integrin interacts with tenascin, which is present in large amounts in the damaged CNS and is the main matrix glycoprotein of the CNS. We find that alpha9 integrin expressed in neurons allows them to regenerate vigorously in tissue culture. When we express alpha9 in sensory neurons in the damaged CNS axons regenerate better than in control animals, but not as floridly as they do in tissue culture. The lower amount of regeneration in vivo is because the inhibitory CNS environment affects integrin trafficking and activation.

We are studying integrin trafficking in axons, and we have found that integrins are trafficked in vesicles identified by Rab11 and Arf6. However, integrins do not get into CNS axons, which is probably one of the main reasons why they do not regenerate. We are working out how to modify CNS axons so that integrins get into their axons.

R. Eva, E. Dassie, P. T. Caswell, G. Dick, C. Ffrench-Constant, J. C. Norman, and J. W. Fawcett. Rab11 and Its Effector Rab Coupling Protein Contribute to the Trafficking of {beta}1 Integrins during Axon Growth in Adult Dorsal Root Ganglion Neurons and PC12 Cells. J.Neurosci. 30 (35):11654-11669, 2010.

M. R. Andrews, S. Czvitkovich, E. Dassie, C. F. Vogelaar, A. Faissner, B. Blits, F. H. Gage, C. Ffrench-Constant, and J. W. Fawcett. Alpha9 integrin promotes neurite outgrowth on tenascin-C and enhances sensory axon regeneration. J.Neurosci 29 (17):5546-5557, 2009.

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