Localization and developmental changes in the neuron-specific cyclin- dependent kinase 5 activator (p35(nck5a)) in the rat brain

Mammalian brains contain a cdc2-like protein kinase which is a heterodimer of cyclin-dependent kinase 5 (Cdk5) and a brain-specific regulatory subunit with a molecular weight of 35,000, named p35(nck5a). Cdk5 has been identified as the major phosphorylating enzyme of tau protein in the brain. In this study, we examined the temporal and spatial expression patterns of p35(nck5a) in the developing rat brain. Northern blot analysis showed that p35(nck5a) messenger RNA expression was low in the brain of 12- day postcoitum rats, and increased to a much higher level from 18 days postcoitum to two weeks after birth, and then declined at three weeks after birth. These developmental changes in p35(nck5a) expression correlated with the changes in Cdk5-associated kinase activity during brain development. These data suggest that p35(nck5a) is the specific activator for Cdk5 in the brain. Immunohistochemical and in situ hybridization studies demonstrated the presence of p35(nck5a) protein in postmitotic neurons but not in glial cells at all stages of brain development, indicating that p35(nck5a) is a neuron-specific protein. In the adult brain, the protein was rich in cell bodies and dendrites, and only very low amounts were detected in axons. In fetal and neonatal brains, however, axonal pathways such as the corpus callosum and external capsule were also stained with anti-p35(nck5a) antibody. Our findings suggest that p35(nck5a) is neuron specific, and a specific activator for Cdk5, and the subcellular localization of the two is strictly regulated depending on brain development. Neuronal Cdc2-like kinase may play key roles in neuronal maturation, synaptic formation, and neuronal plasticity.