Guidance of mesenchymal migration by redistribution and sequestration of Rac1
| Dates: | 13 February 2014 |
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| Times: | 14:00 - 15:00 |
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| What is it: | Seminar |
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| Organiser: | Faculty of Life Sciences |
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| Speaker: | Mark Bass |
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Sustained forward migration through a fibrillar extracellular matrix requires localization of protrusive signals. Contact with fibronectin activates Rac1, but cells require intrinsic polarity to distinguish new contacts, in the direction of migration, from the established matrix contacts that surround the cell body. We identify interactions between Coro1C, RCC2 and Rac1 that focus active Rac1 to a single protrusion. Coro1C redistributes Rac1 from lateral membrane to a protrusive tip and is essential for fibronectin-dependent Rac1 activation. The second component, RCC2, attenuates GEF-mediated Rac1 activation outside the protrusive tip by obscuring the Rac1 switch regions, thus preventing off-axial protrusion. RNAi of these localization signals causes loss of cell polarity that results in shunting migration in 3D culture systems. In vivo, inhibition of the RCC2/Coro1C complex delays the arrival of neural crest derivatives at the correct location in developing zebrafish, demonstrating the critical role in migration guidance. Finally, we find that dysregulated Rac1 signaling is responsible for poor healing efficiency in mouse models, and that we can restore healing rates by manipulating Rac1 regulation exogenously.
Speaker
Mark Bass
Role: Dr
Organisation: School of Biochemistry, University of Bristol
Travel and Contact Information
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B.4208
Michael Smith Building
Manchester
