First published online February 12, 2004
Journal of Cell Science 117, 604e (2004)
© The Company of Biologists Limited
Axonal transport: the phosphorylation connection
The proteins that make up mammalian neurofilaments, a major constituent of the axonal cytoskeleton, are highly phosphorylated. Among other things, this is thought to regulate the transport of newly synthesized neurofilaments from the neuronal cell body to the axons, but the kinases involved are unclear. On p. 933, Thomas Shea and co-workers report that the serine/threonine kinase Cdk5 regulates phosphorylation and axonal transport of neurofilaments. They show that increased Cdk5 activity in cultured chicken dorsal-root-ganglion neurons (achieved by microinjection of Cdk5 and its activator p35 or by transfection of the Cdk5 and p35 genes) increases phosphorylation of the neurofilaments, causes abnormal thickening in the perikaryon, and reduces their axonal transport. Conversely, treatment of the cells with the Cdk5 inhibitor roscovitine reduces neurofilament phosphorylation and enhances their axonal transport. These findings indicate that Cdk5 regulates neurofilament dynamics. Since it is overactivated in amylotrophic lateral sclerosis, this might be one mechanism by which the motor neuron degeneration observed in this disorder arises.
Related articles in JCS:
- Cdk5 regulates axonal transport and phosphorylation of neurofilaments in cultured neurons
- Thomas B. Shea, Jason T. Yabe, Daniela Ortiz, Aurea Pimenta, Patti Loomis, Robert D. Goldman, Niranjana Amin, and Harish C. Pant
JCS 2004 117: 933-941.
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