The Rho-family guanine nucleotide exchange factor GEFT enhances retinoic acid- and cAMP-induced neurite outgrowth

The Rho GTPases are important regulators of neurite outgrowth and pathfinding. We have recently reported that a Rho-family guanine nucleotide exchange factor, GEFT, modulates dendrite spine morphology and basal neurite outgrowth in primary hippocampal neurons and Neuro2A cells, respectively. Here we demonstrate that GEFT protein is highly expressed in all regions of the brain and is highly up-regulated upon treatment of Neuro2A cells with retinoic acid and dibutyric cAMR which promote dendrite and axon-like neurite extensions, respectively. Within retinoic acid-induced neurite extensions, GEFT is localized to actin-enriched regions in the primary neurites, with little or no expression from secondary branches. Dibutyric cAMP-induced neurite extensions are highly concentrated for GEFT at the actin-rich distal tip of the growth cone. Additionally, we demonstrate that GEFT promotes neurite outgrowth in undifferentiated as well as differentiated Neuro2A cells. Together, our data provide new evidence suggesting that GEFT is an important regulator of multiple processes involved in axon and dendrite formation.