Abstract
Neurite outgrowth is an essential process during neuronal differentiation as well as regeneration. Thus, understanding the molecular and cellular control of neurite outgrowth will benefit patients with neuronal diseases and injury. SH2B1β was known to enhance neuronal differentiation, undergo nucleocytoplasmic shuttling and regulate a subset of neurotrophin-induced genes. In this thesis, I provide evidence suggesting that SH2B1β interacts with the transcription factor, signal transducer and activator of transcription 3 (STAT3), by affecting the sub-cellular distribution of STAT3, and increasing serine phosphorylation and the transcriptional activity of STAT3, thus the expression of STAT3 target genes Egr1 and Cdh2 during neuronal differentiation. These findings establish a central role of SH2B1β in orchestrating signaling events to transcriptional activation through interacting and regulating STAT3-containing complexes during neuronal differentiation. Electrical stimulation (ES) has also been shown to enhance both neurite outgrowth and nerve regeneration. In the second part of this thesis, the molecular mechanism is investigated. Our data suggest that ES of 100 mV/mm together with nerve growth factor (NGF) provides optimal effect on promoting neurite outgrowth of PC12 cells. ES promotes NGF-induced neurite outgrowth through modulating the activity of extracellular signal-regulated kinase. These data suggest that combining ES and NGF provides a promising strategy for promoting neurite outgrowth. Taken together, this thesis shows the positive regulation of SH2B1β and ES on neurite outgrowth of PC12 cells.