Neurofilament heavy chain side arm phosphorylation regulates axonal transport of neurofilaments

S Ackerley, P Thornhill, A J Grierson, J Brownlees, B H Anderton, P N Leigh, C E Shaw, C C J Miller

Research output: Contribution to journalArticlepeer-review

165 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)489 - 495
Number of pages7
JournalJournal of Cell Biology
Volume161
Issue number3
DOIs
Publication statusPublished - 12 May 2003

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