The Role of Dense Core Nanoparticles in Regulation of Neuronal Communication

Abstract

The goal of this project is to introduce a novel bottom-up approach to probe the functionality of the dense core nanoparticles by creating artificial dense core nanoparticles from the native proteins.Communication of neurons is happening through the exocytosis process, which is based on vesicular release of neurotransmitters like dopamine. A portion of these vesicles are large dense core vesicles and have the critical function of storing and excreting neurotransmitters or neuropeptides. The so-called dense core is composed of charged polypeptides from the chromogranin family of proteins. This protein matrix accumulates and stores neurotransmitters in high concentrations but the mechanisms of accumulation and release are unknown and highly debated.So far in this work we have developed a model system for the first time as artificial dense core nanoparticles. The synthesized dense core protein nanoparticles are made of chromogranin A, which is the main protein, located in large dense core vesicles. This protein is proposed to involve in the storage of neurotransmitters, Ca2+, and ATP within secretory vesicle. To explore the interactions between dense core proteins and neurotransmitters like dopamine, we are using isothermal titration calorimetry (ITC). By this study we could determine the binding affinity and stoichiometry of neurotransmitter storage under various physiological conditions, such as the pH gradient between the interior and exterior of the secretory vesicle, and the presence of other small physiological relevant molecules such as calcium and ATP.