Neurofilaments
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].
References:
- 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
- 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
- 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
