抄録
Cyclin-dependent kinase 5 (Cdk5) is a multifunctional Ser/Thr protein kinase activated by binding to its activator p35 or p39, which is expressed predominantly in neurons. Cdk5 is shown to be involved in neuronal migration during brain development, synaptic activity in matured neurons, and neuronal cell death in aged brains. However, exact roles of Cdk5 in those neuronal activities have not been answered yet. Cellular localization would be critical to understand the detailed functions of Cdk5/p35 or Cdk5/p39. p35 or p39 activator controls the cellular localization as well as the kinase activity. The Cdk5/p35 and Cdk5/p39 complexes bind to plasma membranes and Golgi apparatus via myristoylation at the N-terminal Gly of p35 or p39 that may compartmentalize the active Cdk5 complexes in the cytoplasm. When Gly is mutated to Ala, Cdk5/p35 and Cdk5/p39 become soluble in the cytoplasm and then is translocated into nucleus. This mislocalization is observed at the time of neuronal cell death. For example, endoplasmic reticulum (ER) stress deregulates the Cdk5 activity by cleavage of p35 to p25 with calpain. The cleavage of p35 changes the cellular distribution of active Cdk5, stabilizes the p25/Cdk5 complex, and stimulates the kinase activity of Cdk5, thereby allowing potentially aberrant phosphorylation of neuronal proteins, which would adversely affect the survival of neurons. We would also like to discuss on its localization in relation to membrane trafficking in living neurons. [J Physiol Sci. 2006;56 Suppl:S35]
