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First published online 3 February 2004
doi: 10.1242/jcs.00785

Journal of Cell Science 117, 933-941 (2004)
Published by The Company of Biologists 2004
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Research Article

Cdk5 regulates axonal transport and phosphorylation of neurofilaments in cultured neurons

Thomas B. Shea1,*, Jason T. Yabe1, Daniela Ortiz1, Aurea Pimenta1,2, Patti Loomis3, Robert D. Goldman3, Niranjana Amin4 and Harish C. Pant1,4

1 Center for Cellular Neurobiology and Neurodegeneration Research, Departments of Biological Sciences and Biochemistry, University of Massachusetts, Lowell, One University Avenue, Lowell, MA 01854, USA
2 Department of Pharmacology, Vanderbilt University, Nashville, TN 37232-8548, USA
3 Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, IL 60611, USA
4 Laboratory of Neurochemistry, NIH, NINDS, Bethesda, MD 20892, USA

* Author for correspondence (e-mail: thomas_shea{at}uml.edu)

Accepted 22 July 2003

Phosphorylation has long been considered to regulate neurofilament (NF) interaction and axonal transport, and, in turn, to influence axonal stability and their maturation to large-caliber axons. Cdk5, a serine/threonine kinase homologous to the mitotic cyclin-dependent kinases, phosphorylates NF subunits in intact cells. In this study, we used two different haptenized NF subunits and manipulated cdk5 activity by microinjection, transfection and pharmacological inhibition to monitor the effect of Cdk5-p35 on NF dynamics and transport. We demonstrate that overexpression of cdk5 increases NF phosphorylation and inhibits NF axonal transport, whereas inhibition both reduces NF phosphorylation and enhances NF axonal transport in cultured chicken dorsal-root-ganglion neurons. Large phosphorylated-NF `bundles' were prominent in perikarya following cdk5 overexpression. These findings suggest that Cdk5-p35 activity regulates normal NF distribution and that overexpression of Cdk5-p35 induces perikaryal accumulation of phosphorylated-NFs similar to those observed under pathological conditions.

Key words: cdk5, p35, Neurofilaments, Axonal transport, Phosphorylation, Neurofibrillary pathology


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