Tropomyosin binding is essential for tropomodulin to regulate spine reorganization

Primary author: Balaganesh Kuruba
Faculty sponsor: Alla Kostyukova

Primary college/unit: Voiland College of Engineering and Architecture
Campus: Pullman

Abstract:

Formation of connections between neurons (synapses) is essential for proper brain function. Synapses are formed by axon terminals and dendrites (spines and shafts). Spine formation and reorganization depend on actin polymerization and depolymerization. Disruption in this process affects spine formation and thereby impairs many brain cognitive functions. Tropomodulin is a protein which controls polymerization of actin by binding to actin via tropomyosin, another actin binding protein. In our study, we showed that disruption of tropomyosin-binding ability of tropomodulin 2 resulted in changes in spine morphology, overall reduction of spine density and average spine length in primary hippocampal neurons. Tropomodulin interacts with two tropomyosin molecules during regulation of actin polymerization. No atomic structural information is available for the binding interface between tropomodulin and tropomyosin. Establishing the structure is critical to understand the actin dynamics regulation mechanism by tropomodulin. Using circular dichroism and nuclear magnetic resonance spectroscopic studies, we showed that tropomyosin peptide containing first 44 N-terminal residues is the optimal fragment to form respective stable complexes with the two tropomyosin-binding sites in tropomodulin.