Neurofilament subunit (NFL) head domain phosphorylation regulates axonal transport of neurofilaments

Eur J Cell Biol. 2009 Apr;88(4):193-202. doi: 10.1016/j.ejcb.2008.11.004. Epub 2009 Jan 14.

Abstract

Neurofilaments are the intermediate filaments of neurons and are synthesised in neuronal cell bodies and then transported through axons. Neurofilament light chain (NFL) is a principal component of neurofilaments, and phosphorylation of NFL head domain is believed to regulate the assembly of neurofilaments. However, the role that NFL phosphorylation has on transport of neurofilaments is poorly understood. To address this issue, we monitored axonal transport of phosphorylation mutants of NFL. We mutated four known phosphorylation sites in NFL head domain to either preclude phosphorylation, or mimic permanent phosphorylation. Mutation to preclude phosphorylation had no effect on transport but mutation of three sites to mimic permanent phosphorylation inhibited transport. Mutation of all four sites together to mimic permanent phosphorylation proved especially potent at inhibiting transport and also disrupted neurofilament assembly. Our results suggest that NFL head domain phosphorylation is a regulator of neurofilament axonal transport.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axonal Transport*
  • Axons / metabolism*
  • Cells, Cultured
  • Intermediate Filaments / genetics
  • Intermediate Filaments / metabolism*
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Neurons / cytology
  • Neurons / metabolism*
  • Phosphorylation
  • Rats
  • Transfection

Substances

  • Mutant Proteins