Christian, Bryan
Mentor: Dr. Margot Quinlan
Actin is an essential protein that forms into filaments within cells, and is for many vital cellular functions, including cell division, muscle contraction, cell motility, and cell polarity. Mammals have six different actin isoforms: four muscle and two non-muscle. These six isoforms are no less than 93% identical between each other, yet each has distinct roles within cells. Additionally, there is evidence of isoform specificity by formins, proteins which nucleate and elongate actin filaments. The Quinlan lab previously found that formins Fhod1 and Delphilin both preferentially nucleate muscle actin rather than non-muscle actin. While it has been shown that the different actin isoforms are selectively utilized in cells, there is still little known about how isoforms are specifically selected by formins and other actin-binding proteins.
My research focuses on understanding how formins selectively discriminate between different actin isoforms and how this selectivity contributes to the functions of both formins and actin. This will be carried out by creating formin chimera, which will be non-isoform-specific formins with specific subdomains replaced from an isoform-specific formin. This will help us understand which subdomains interact with non-identical residues in actin. I will also investigate which amino acids and post-translational modifications in actin are important for this selectivity by introducing mutations in suspected residues. This research will help us understand how actin isoforms are able to form distinct structures within the same cell despite being nearly identical to one another.
