Neuronal adaptor FE65 stimulates Rac1-mediated neurite outgrowth by recruiting and activating ELMO1.

摘要: Neurite outgrowth is a crucial process in developing neurons for neural network formation. Understanding the regulatory mechanisms of neurite essential strategies to stimulate regeneration after nerve injury and neurodegenerative disorders. FE65 brain-enriched adaptor that stimulates Rac1-mediated elongation. However, precise mechanism by which promotes remains elusive. Here, we show ELMO1, subunit ELMO1-DOCK180 bipartite Rac1 guanine nucleotide exchange factor (GEF), interacts with N-terminal region. Overexpression and/or ELMO1 enhances, whereas knockdown or inhibits, activation. The effect alone together attenuated an double mutation disrupts FE65-ELMO1 interaction. Notably, found activate diminishing intramolecular autoinhibitory interaction promote targeting plasma membrane, where activated. We also FE65, DOCK180 form tripartite complex. Knockdown reduces stimulatory on activation outgrowth. Thus, identify novel recruiting activating ELMO1.