Nedd5 is a septin protein enriched in brain and associates with the exocyst complex, a protein complex required for neurite outgrowth in neuroendocrine PCl2 cells. In this study, we further investigate the association between Nedd5 and the exocyst complex as well as the role of Nedd5 in neurite outgrowth in differentiating PCl2 cells. The endogenous Nedd5 is enriched at the perinuclear region in undifferentiated PCl2 cells and radiates outward, from the perinuclear region toward the growth cone, upon NGF-induced PCl2 neuronal differentiation. Nedd5, as well as other septin proteins, co-immunoprecipitates with the exocyst complex and tubulin from rat brain lysate. Interestingly, the over-expression of a GTPase-defective Nedd5 mutant promotes aberrant neurite sprouting in PCl2 cells. These results demonstrate that Nedd5 and other septin proteins are associated with both the exocyst complex and microtubules and uncover a putative role for the Nedd5 GTPase activity in neurite outgrowth. Taken together, these findings suggest that Nedd5 may be required for polarized neurite outgrowth, perhaps, by facilitating the exocyst complex function during neuronal differentiation.
All Science Journal Classification (ASJC) codes
- Exocyst complex
- Neurite outgrowth
- Neuronal differentiation