Preliminary Exploration Of The Function Of CDK5 In Auditory System

Cyclin dependent kinase5,a special member of cyclin dependent kinase family,but does not participate in the regulation of cell cycle.The present study of CDK5 mainly focus on the field of neuron,including the migration of neuron,the extension of dendritic,apoptosis and autophagy of neuron.CDK5 plays an important rolein the pathologic process of Alzheimer disease,Parkinson disease and other neurological degenerative disease.CDK5 depends on its kinase activity to phosphorate its Substrate to participate in various activities.CDK5 must coexist with its activator to phosphorate other proteins.p35 and p39 are the common activator of CDK5.CDK5 knockout mice is lethal owing to structural defeat of cerebral cortex,while p35 or p39 single knockout mice is not lethal,and only p35 and pP39 double knockout mice has the same phenotype.p35 and p39 can be spliced into p25 and p29 by calpain.It is can be one of the important means to regulate this activity of CDK5.The auditory system is a peripheral sensory system and one of the main sources of our access to outside information.CDK5 is a universal expression protein,which distributed in various tissues.While p35 and p39 are neuron specific proteins,which rarely found in other tissues.We detected the expreesion of CDK5 and p35,p39 in the inner ear,and we found that the expression of CDK5 was much rich,while no expression or only a few expression of p35 and p39 was detected.This shows that the main activator of CDK5 in the inner ear is not p33 r p339.We used the yeast two hybrid system screening the chicken inner ear library to explore the protein which interacts with CDK5.We found CCNI and CCNI2.It suggested that CDK5 may be activated by these two proteins mainly in the inner ear.In previous study,CCNI activates CDK5 has been reported.CCNI2 is the ortholog of CCNI and there is no biological function of this gene has been reported.We verify that CDK5 interact with CCNI and CCNI2 by Co-IP and Co-localization.Finally,we explored the effect of CCNI2 on CDK5 kinase activity by the method of kinase array experiment.This study lays a good foundation for our understanding of the function and regulatory mechanism of CDK5 in the inner ear.Because the time limit,the animal experiment is not yet complete in vivo.Further study is needed to understand the physiological function of CDK5 and CCNI,CCNI2 in auditory transduction by gene knockout mice and other methods.