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 heterod imer of cyclin-dependent kinase 5 (Cdk5) and a brain-specific regulato ry subunit with a molecular weight of 35,000, named p35(nck5a). Cdk5 h as been identified as the major phosphorylating enzyme of tau protein in the brain. In this study, we examined the temporal and spatial expr ession patterns of p35(nck5a) in the developing rat brain. Northern bl ot analysis showed that p35(nck5a) messenger RNA expression was low in the brain of 12-day postcoitum rats, and increased to a much higher l evel from 18 days postcoitum to two weeks after birth, and then declin ed at three weeks after birth. These developmental changes in p35(nck5 a) expression correlated with the changes in Cdk5-associated kinase ac tivity 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 o f brain development, indicating that p35(nck5a) is a neuron-specific p rotein. In the adult brain, the protein was rich in cell bodies and de ndrites, and only very low amounts were detected in axons. In fetal an d neonatal brains, however, axonal pathways such as the corpus callosu m and external capsule were also stained with anti-p35(nck5a) antibody . Our findings suggest that p35(nck5a) is neuron specific, and a speci fic 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. Copyright (C) 1996 IBRO. Published by Elsevi er Science Ltd.