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A Tale of the Good and Bad: Remodeling of the Microtubule Network in the Brain by Cdk5

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Abstract

Cdk5, a cyclin-dependent kinase family member, is a global orchestrator of neuronal cytoskeletal dynamics. During embryogenesis, Cdk5 is indispensable for brain development. In adults, it is essential for numerous neuronal processes, including higher cognitive functions such as learning and memory formation, drug addiction, pain signaling, and long-term behavior changes through long-term potentiation and long-term depression, all of which rely on rapid alterations in the cytoskeleton. Cdk5 activity becomes deregulated in various brain disorders, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, attention-deficit hyperactivity disorder, epilepsy, schizophrenia, and ischemic stroke; these all result in profound remodeling of the neuronal cytoskeleton. This Commentary specifically focuses on the pleiotropic contribution of Cdk5 in regulating neuronal microtubule remodeling. Because the vast majority of the physiological substrates of Cdk5 are associated with the neuronal cytoskeleton, our emphasis is on the Cdk5 substrates, such as CRMP2, stathmin, drebrin, dixdc1, axin, MAP2, MAP1B, doublecortin, kinesin-5, and tau, that have allowed to unravel the molecular mechanisms through which Cdk5 exerts its divergent roles in regulating neuronal microtubule dynamics, both in healthy and disease states.

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Acknowledgments

This work was supported by grant from the National Institutes of Health (NIAR21AG 47447) to KS and DKL. The authors sincerely thank Bryan Maloney (IUPUI) for his critical reading and helpful comments.

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  1. Department of Chemistry and Purdue University Center for Cancer Research, 560 Oval Drive, West Lafayette, IN, 47907, USA

    Kavita Shah

  2. Departments of Psychiatry and Medical & Molecular Genetics, Institute of Psychiatric Research, Neuroscience Research Center, Indiana University School of Medicine, 320 W. 15th Street, Indianapolis, IN, 46202-2266, USA

    Debomoy K. Lahiri

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Shah, K., Lahiri, D.K. A Tale of the Good and Bad: Remodeling of the Microtubule Network in the Brain by Cdk5. Mol Neurobiol 54, 2255–2268 (2017). https://doi.org/10.1007/s12035-016-9792-7

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