| Septins constitute a family of evolutionarily conserved proteins that were first discovered for their involvement in cell division. Recently, they are also found to be increasingly important in various neurodegenerative states, such as Parkinson's and Alzheimer's diseases. Molecular mechanisms underlying the function of septin proteins in the nervous system, however, remain largely unknown. Work from this thesis revealed that a member of the septin family, SEPT2, is important for exocytosis underlying neurite outgrowth in PC12 cells. SEPT2 has a similar tissue distribution and developmental expression profile as that of sec15, a subunit of the exocyst complex which has been found to be required for exocytosis. In undifferentiated PC12 cells, SEPT2 exhibited perinuclear enrichment, as observed for exocyst subunits. Upon neuronal differentiation, SEPT2, like exocyst subunits, redistributes from its perinuclear enrichment to the neurites and the growth cones. Knockdown of SEPT2 disrupted the perinuclear enrichment of exocyst subunits, decreased the protein levels of exocyst subunits. Under this condition, neurite outgrowth and the insertion of protein into the plasma membrane of PC12 cells were inhibited. These results suggest a novel mechanism by which SEPT2 can mediate and/or regulate exocytosis underlying neurite outgrowth through its direct or indirect association with the exocyst complex. |
