CHE 598 Seminar: “Regulation of Actin Dynamics at Thin Filament Pointed Ends in the Heart”, Presented by: Dr. Mert Colpan
About the event
BIOGRAPHY:
Dr. Mert Colpan received his B.S. in Bioengineering in 2011 from a dual-degree program between Istanbul Technical University and Montana State University and his Ph.D. in Bioengineering under Prof. Alla Kostyukova’s supervision in 2016 from Washington State University. He published 8 journal articles in graduate school (5 as the first author) and was a frequent presenter at national meetings. After obtaining his degree, Dr. Colpan joined Prof. Carol Gregorio’s laboratory at the University of Arizona in 2016 as a postdoctoral research associate and is currently a research scientist in the same lab. He received numerous awards for his postdoctoral work from organizations including the Sarver Heart Center and American Heart Association. Dr. Colpan’s research focuses on a comprehensive understanding of mechanisms that are critical for precisely specifying and maintaining sarcomeric structure during heart development in health and disease. Specifically, his projects focus on: 1) understanding the cellular and molecular mechanisms involved in the assembly, regulation and maintenance of contractile proteins in cardiac muscle; 2) deciphering how cells regulate the length and polarity of actin filaments in normal and diseased muscle; 3) development of novel in vitro and in vivo models of de novo cardiac myofibril assembly and 4) discovering the underlying reasons for cardiomyopathy development from genetic mutations found in human patients. His studies implement a multitude of physiological levels including patient samples, mice, isolated hearts, and cell culture, as well as the single molecule level – to study the mechanisms contributing to de novo thin filament assembly and disease progression. For his work, Dr. Colpan utilizes a wide-range of multidisciplinary approaches including mouse models, advanced cell biology, confocal and deconvolution immunofluorescence microscopy, super-resolution microscopy, live cell imaging, in vivo expression of proteins via adeno-associated virus, echocardiography analysis, FRAP, fluorescence spectroscopy, biophysical analysis of myofilament force and calcium measurements. His future research goals are discovering common pathophysiologies of cardiomyopathy and creating potential therapeutic targets for treating and preventing heart diseases.
ABSTRACT:
Striated muscle is intricately designed for efficient muscle contractions. The precise assembly of actin-based thin filaments is crucial for muscle structure and function. Dysregulation of actin polymerization at thin filament pointed ends results in skeletal and cardiac myopathies. Tmod1 and Lmod2 have been known to be the exclusive regulators of thin filament lengths by modulating actin dynamics at the pointed ends in cardiac muscle. We recently discovered adenylyl cyclase-associated protein 2 (CAP2) as a unique third component of thin filament pointed ends. Although mutations in the CAP2 gene in human patients lead to severe heart disease and failure, CAP2’s exact role in the heart was largely unknown. We identified CAP2 as a crucial contributor to actin polymerization in cardiac muscle cells as it depolymerizes and inhibits actin incorporation into thin filaments. CAP2 plays an essential role in heart development by regulating actin assembly and α-actin composition in mature thin filaments. Identification of CAP2’s multifunctional roles provides missing links in our understanding of how thin filament architecture is regulated in striated muscle and explains why CAP2 leads to severe muscle disease when mutated.