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Title: CYRI-A is recruited to macropinocytic cups and mediates integrin uptake, limiting invasive migration
Author: Le, Hoang Anh
ISNI:       0000 0005 0286 8644
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2021
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In this thesis, we explore the function of a novel protein called CYRI-A through the use of biochemical, biophysical and microscopical techniques. CYRI-A belongs to the group of protein of unknown function. The previous work from our lab described its cousin protein CYRI-B to be the first negative regulator of the Scar/WAVE complex, hence regulating cell migration. Here, through the use of microscopical analysis, we unexpectedly discover the function of CYRI-A as a novel regulator of macropinocytosis. We found that CYRI-A is transiently recruited to the macropinocytic cups, at which it binds and sequesters active Rac1 and suppressing actin polymerisation. This drives the maturation and completion of the macropinocytic cups. In cancer cells, we also found that CYRI-dependent macropinocytosis is important for integrin internalisation. Thus, cells lacking CYRIs express a higher level of surface integrins, which affects its migration, adhesion, and invasion capacity. In a collaboration with the Ismail's group, we also solved the crystal structure of CYRI-B, and discovered that CYRIs are also able to dimerise with each other. This dimerisation directly competes with active Rac1 binding, adding an additional layer of regulation to CYRI. Overall, this thesis provides a careful analysis of the kinetics and localisation of CYRI-A and its novel function as a regulator of macropinocytosis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: QH301 Biology ; RC0254 Neoplasms. Tumors. Oncology (including Cancer)