Neurofilament heavy chain side arm phosphorylation regulates axonal transport of neurofilaments

2003/05/12 by Steven Ackerley, Paul Thornhill, Andrew J. Grierson +5 · 25 citations
Biochemistry, Genetics and Molecular Biology · #Skin and Cellular Biology Research #Cellular Mechanics and Interactions #Kruppel-like factors research

paper · pdf · doi:10.1083/jcb.200303138

Abstract

Neurofilaments possess side arms that comprise the carboxy-terminal domains of neurofilament middle and heavy chains (NFM and NFH); that of NFH is heavily phosphorylated in axons. Here, we demonstrate that phosphorylation of NFH side arms is a mechanism for regulating transport of neurofilaments through axons. Mutants in which known NFH phosphorylation sites were mutated to preclude phosphorylation or mimic permanent phosphorylation display altered rates of transport in a bulk transport assay. Similarly, application of roscovitine, an inhibitor of the NFH side arm kinase Cdk5/p35, accelerates neurofilament transport. Analyses of neurofilament movement in transfected living neurons demonstrated that a mutant mimicking permanent phosphorylation spent a higher proportion of time pausing than one that could not be phosphorylated. Thus, phosphorylation of NFH slows neurofilament transport, and this is due to increased pausing in neurofilament movement.

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