Table of Contents Author Guidelines Submit a Manuscript
Journal of Amino Acids
Volume 2012 (2012), Article ID 382107, 10 pages
Review Article

Neurofilament Phosphorylation during Development and Disease: Which Came First, the Phosphorylation or the Accumulation?

1Division of Biological Sciences, University of Missouri-Columbia, Columbia, MO 65211, USA
2Bond Life Sciences Center, University of Missouri-Columbia, Columbia, MO 65211, USA

Received 17 November 2011; Accepted 31 January 2012

Academic Editor: Ewa A. Bienkiewicz

Copyright © 2012 Jeffrey M. Dale and Michael L. Garcia. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Posttranslational modification of proteins is a ubiquitous cellular mechanism for regulating protein function. Some of the most heavily modified neuronal proteins are cytoskeletal proteins of long myelinated axons referred to as neurofilaments (NFs). NFs are type IV intermediate filaments (IFs) that can be composed of four subunits, neurofilament heavy (NF-H), neurofilament medium (NF-M), neurofilament light (NF-L), and α-internexin. Within wild type axons, NFs are responsible for mediating radial growth, a process that determines axonal diameter. NFs are phosphorylated on highly conserved lysine-serine-proline (KSP) repeats located along the C-termini of both NF-M and NF-H within myelinated axonal regions. Phosphorylation is thought to regulate aspects of NF transport and function. However, a key pathological hallmark of several neurodegenerative diseases is ectopic accumulation and phosphorylation of NFs. The goal of this review is to provide an overview of the posttranslational modifications that occur in both normal and diseased axons. We review evidence that challenges the role of KSP phosphorylation as essential for radial growth and suggests an alternative role for NF phosphorylation in myelinated axons. Furthermore, we demonstrate that regulation of NF phosphorylation dynamics may be essential to avoiding NF accumulations.