Expression of neuronal proteins in a differentiating human neuroblastoma cell line (IMR32): Insights into neuronal development and disease

The acquisition of a neuronal phenotype by exposure to specific intrinsic and extrinsic signals is a property of neuroblasts, adult neural stem cells, and the IMR32 human neuroblastoma cell line. As several complex psychiatric, cognitive, and neurological human disorders such as schizophrenia, autism, and some epilepsies are now being approached as neurodevelopmental disorders, it is critical to understand the normal course of neuronal differentiation with the long term goal of strategic intervention and management of the chronic and debilitating diseases. In my thesis, we explore the use of IMR32 cells as a simplified and accessible model system for studying neuronal differentiation and exploring the expression of proteins with synaptic functions; specifically, secretory proteins, voltage-dependent calcium channels, and proteins implicated in growth cone formation and neurite formation. We also explore the expression of MeCP2 and use a novel antibody to neural cell adhesion molecule (NCAM) 180 kDa isoform to monitor the acquisition of a neuronal phenotype in parallel to other markers of synaptic function. The biochemical analyses of VDCC assembly in IMR32 cells and expression of VDCC subunits have identified how alpha 1 and beta subunits are assembled in a single cell type. Thus, the use of differentiated IMR32 cells as a cell model offers a unique cell population for future study on neuronal differentiation and neuronal proteins involved with neurodevelopmental disorders in vitro.