Cdk5: A Key Player at Neuronal Synapse with Diverse Functions

The development and function of neuronal synapses are orchestrated by various extrinsic factors through intracellular signaling cascades that often involve protein kinases. One important kinase at the synapse is the proline-directed serine/ threonine kinase Cdk5. Although early pharmacological and genetic studies have pointed out the critical role of Cdk5 in regulating synapse function, the precise mechanisms have only been unraveled in recent years through the identification and characterization of multiple substrates. Emerging studies also indicate that Cdk5 dysregulation is linked to mitochondrial dysfunction. This review focuses on recent progress in our understanding of the multiple roles of Cdk5 in mitochondrial function, synapse development and plasticity through phosphorylation of specific substrates at different cellular compartments.