Date of Award

2023

First Advisor

Amy Smith

Second Advisor

David Myers

Third Advisor

Jessica Henty-Ridilla

Abstract

IQ-motif containing GTPase activating protein 1 (IQGAP1) is a large actin-binding protein that interacts with the sides of actin filaments. When IQGAP1 binds to the sides of actin filaments, it organizes them into bundles, which are important for cell motility, cell adhesion, and cytokinesis. This bundling activity is mediated primarily by its Nterminal Calponin Homology Domain, though the exact residues needed for this activity are not known. To investigate the residues that are involved in this side-binding activity, both in-vitro TIRF microscopy assays and cell models were utilized. Results show that when WT-IQGAP1 is mutated at 4 residues that are thought to be involved in this actinbinding activity (FL-IQGAP1-GFRR), it creates thinner actin bundles in vitro. Our results also suggest that FL-IQGAP1-GFRR has an effect on cells in vivo, creating stress fibers with fewer actin filaments and possibly promoting filopodia formation, but potentially having little effect on leading-edge dynamics at lamellipodia. It was also found that FL-IQGAP1-GFRR may affect microtubule dynamics, as it was found to create wider microtubules in vivo. Background information on the major components of the cytoskeleton, its major functions within the cell, and links to disease, as well as IQGAP1’s roles within the cell and links to disease are also described in addition to these experimental results.

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