Pathway Map Details

Cytoskeleton remodeling_Neurofilaments

view in full size
| open in MetaCore

Object list (links open in MetaCore):

DCTN1(p150Glued), DCTN2, Dynactin complex, BPAG1, Tubulin alpha, NEFM, NEFL, Kinesin heavy chain, Plectin 1, Vimentin, CDK5R1 (p35), Tubulin gamma, Alpha-internexin, CDK5, Tubulin heterodimers (in microtubules), MUNC18, Tubulin gamma 1, NEFH, Actin cytoskeletal, Peripherin, GFAP, Desmuslin, Tubulin beta, Desmin, Nestin



Cytoskeleton of most eukaryotic cells consists of three distinct, yet interconnected, filament systems: actin filaments, microtubules and intermediate filaments (IF). IF network is critically involved in cell shape control and imparts intracellular mechanical strength.

The family of IF proteins has five sub-families: four of them are localized in the cytoplasm and one resides in the nucleus. Cytoplasmic IF proteins such as Vimentin, Desmin, GFAP, Peripherin, Nestin, Desmuslin, alpha-Internexin, Neurofilament triplet proteins ( NEFL, NEFM, NEFH ) form diverse heteropolymers.

Expression patterns of cytoplasmic IFs are cell- and tissue-type specific [1]. Neurofilaments is the principal intermediate filament type expressed by neurons. They are formed by co-assembly of three subunits: NEFL, NEFM, and NEFH.

Peripherin is another IF protein expressed mostly in neurons of the peripheral nervous system. In contrast to neurofilaments, Peripherin can self-assemble to establish an intermediate filament network. In some cases, Peripherin can assemble with NEFL. It was suggested that perturbations in the stoichiometry of neurofilaments can impact Peripherin assembly [2].

Neurofilaments are important protein cargoes for actin -associated motors, such as myosin, and microtubule -associated motor, such as kinesin in a complex with Dynactin. These motors are responsible for timely delivery of neural IF particles and squiggles to all regions of the neuron. Long neural IFs move along neuritis, albeit more slowly than the precursors.

Munc18, a neuron-specific protein, is independently identified as a syntaxin-binding protein, that regulates kinase activity of cyclin dependent kinase 5 ( CDK5 ). Munc18 binds to NEFM and NEFH suggesting its role in the neuron cytoskeletal dynamics.

IF networks are cross-linked by Plectin 1 and BPAG1 that maintain cell and tissue integrity by coordinated interconnection of three distinct cytoskeletal filament systems [3].


  1. Strelkov SV, Herrmann H, Aebi U
    Molecular architecture of intermediate filaments. BioEssays : news and reviews in molecular, cellular and developmental biology 2003 Mar;25(3):243-51
  2. Beaulieu JM, Robertson J, Julien JP
    Interactions between peripherin and neurofilaments in cultured cells: disruption of peripherin assembly by the NF-M and NF-H subunits. Biochemistry and cell biology = Biochimie et biologie cellulaire 1999;77(1):41-5
  3. Helfand BT, Chang L, Goldman RD
    Intermediate filaments are dynamic and motile elements of cellular architecture. Journal of cell science 2004 Jan 15;117(Pt 2):133-41