Fig. 4.

Cdk5 activates the Cdc42 pathway via TrkB and 5-HT6 receptor phosphorylation, leading to dendrite growth and neuronal differentiation, respectively. BDNF-induced TrkB activation facilitates Cdk5 activation via Y15 phosphorylation, which in turn phosphorylates TrkB at S478 in the juxtamembrane region. Subsequently, TrkB activates Cdc42, causing dendrite outgrowth and extension. Cdk5 constitutively associates with the C-terminal domain of 5-HT6R and phosphorylates it at S350, leading to the activation of the Cdc42 pathway, promoting neurite outgrowth. This phosphorylation event also increases the expression of VGCCs, although it remains undetermined whether it is a Cdc42-dependent or Cdc42-independent process. Both neurite outgrowth and VGCC upregulation are hallmarks of neuronal differentiation