期刊
JOURNAL OF CELL BIOLOGY
卷 161, 期 3, 页码 489-495出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200303138
关键词
neurofilament proteins; axonal transport; amyotrophic lateral sclerosis; Alzheimer's disease; Cdk5/p35
类别
资金
- Medical Research Council [G0000749] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
- MRC [G0000749] Funding Source: UKRI
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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