C dk5 regulates multiple cellular events in neural development, function and disease

Cyclin‐dependent kinases ( CDK s) generally regulate cell proliferation in dividing cells, including neural progenitors. In contrast, an unconventional CDK , C dk5, is predominantly activated in post‐mitotic cells, and involved in various cellular events, such as microtubule and actin cytoskeletal organization, cell–cell and cell–extracellular matrix adhesions, and membrane trafficking. Interestingly, recent studies have indicated that C dk5 is associated with several cell cycle‐related proteins, Cyclin‐ E and p27 kip1 . Taking advantage of multiple functionality, C dk5 plays important roles in neuronal migration, layer formation, axon elongation and dendrite arborization in many regions of the developing brain, including cerebral cortex and cerebellum. C dk5 is also required for neurogenesis at least in the cerebral cortex. Furthermore, C dk5 is reported to control neurotransmitter release at presynaptic sites, endocytosis of the NMDA receptor at postsynaptic sites and dendritic spine remodeling, and thereby regulate synaptic plasticity and memory formation and extinction. In addition to these physiological roles in brain development and function, C dk5 is associated with many neurodegenerative diseases, such as A lzheimer's disease, P arkinson's disease and amyotrophic lateral sclerosis. In this review, I will introduce the physiological and pathological roles of C dk5 in mammalian brains from the viewpoint of not only in vivo phenotypes but also its molecular and cellular functions.