Full length talin stimulates integrin activation and axon regeneration

Molecular and Cellular Neurosciences
Chin Lik TanJames W Fawcett

Abstract

Integrin function is regulated by activation involving conformational changes that modulate ligand-binding affinity and downstream signaling. Activation is regulated through inside-out signaling which is controlled by many signaling pathways via a final common pathway through kindlin and talin, which bind to the intracellular tail of beta integrins. Previous studies have shown that the axon growth inhibitory molecules NogoA and chondroitin sulfate proteoglycans (CSPGs) inactivate integrins. Overexpressing kindlin-1 in dorsal root ganglion (DRG) neurons activates integrins, enabling their axons to overcome inhibitory molecules in the environment, and promoting regeneration in vivo following dorsal root crush. Other studies have indicated that expression of the talin head alone or with kindlin can enhance integrin activation. Here, using adult rat DRG neurons, we investigate the effects of overexpressing various forms of talin on axon growth and integrin signaling. We found that overexpression of the talin head activated axonal integrins but inhibited downstream signaling via FAK, and did not promote axon growth. Similarly, co-expression of the talin head and kindlin-1 prevented the growth-promoting effect of kindlin-1, suggestin...Continue Reading

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Citations

Nov 9, 2016·Journal of Forensic and Legal Medicine·Zahra K CampellGulnaz T Javan
Feb 16, 2018·Biological Reviews of the Cambridge Philosophical Society·Bart NieuwenhuisJames W Fawcett
Aug 6, 2017·The AAPS Journal·Jelena M Janjic, Vijay S Gorantla
Feb 9, 2020·Cells·Diana C Muñoz-LassoPilar Gonzalez-Cabo
Feb 16, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yifan WangJun Guo
Mar 15, 2018·Cells·Menghon Cheah, Melissa R Andrews

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