Neurofilament


Neurofilament
neurofilament, light polypeptide 68kDa
Identifiers
Symbol NEFL
Entrez 4747
HUGO 7739
OMIM 162280
RefSeq NM_006158
UniProt P07196
Other data
Locus Chr. 8 p21
neurofilament, heavy polypeptide 200kDa
Identifiers
Symbol NEFH
Entrez 4744
HUGO 7737
OMIM 162230
RefSeq NM_021076
UniProt P12036
Other data
Locus Chr. 22 q12.1-13.1
neurofilament 3 (150kDa medium)
Identifiers
Symbol NEF3
Entrez 4741
HUGO 7734
OMIM 162250
RefSeq NM_005382
UniProt P07197
Other data
Locus Chr. 8 p21

Neurofilaments are the 10 nanometer (10nm) intermediate filaments found specifically in neurons. They are a major component of the cell's cytoskeleton, and provide support for normal axonal radial growth (i.e. increases in axon's diameter). Neurofilaments are composed of polypeptide chains or subunits that are related structurally to the intermediate filaments of other tissues such as keratin subunits, which make 10nm filaments expressed specifically in epithelia. The family of proteins making intermediate filaments is divided into 5 major classes, the keratins forming the classes I and II. Class III contains the proteins Vimentin, Desmin, Peripherin and Glial Fibrillary Acidic Protein (GFAP). The major neurofilament subunits occupy the class IV family of intermediate filaments. Finally class V contains the nuclear lamins.

Contents

Classification

Subunit Proteins of Neurofilaments

The three major neurofilament subunits were discovered from studies of proteins transported down axons. Proteins are synthesized within the cell body, and hence they must travel along an axon to reach their final destination. The names given to the three major neurofilament subunits are based upon the apparent molecular weight of the mammalian subunits on SDS-PAGE:

  • the light or lowest (NF-L) runs at 68-70kDa
  • the medium or middle (NF-M) runs at about 145-160kDa
  • the heavy or highest (NF-H) runs at 200-220kDa

The SDS-PAGE molecular weights vary between mammalian species, with larger species usually having larger proteins. The real molecular weights of these proteins are considerably lower than the SDS-PAGE estimates, particularly in the case of NF-H and NF-M. This is due to the highly charged C-terminal regions of the molecules. Neurofilaments are found in vertebrate neurons in especially high concentrations along the axons, where they appear to regulate axonal diameter.

A fourth class IV subunit alpha-internexin, a.k.a. NF66, is found in association with NF-L, NF-M and NF-H in many situations and is expressed earlier in development than the other neurofilament proteins.

A fifth protein belonging to class IV, Nestin, is found in developing neurons and glia, and the presence of this protein is widely used to define neural stem cells. This protein is lost as development proceeds.

The class III intermediate filament protein subunit peripherin is found in neurofilaments along with the class IV subunits in a few neurons, mostly in the peripheral nervous system. Finally another class III intermediate filament subunit, vimentin, is found in developing neurons and a few very unusual neurons in the adult in association with class IV proteins, such as the horizontal neurons of the retina.

In the adult mammal neurofilament subunit proteins coassemble in vivo, forming a heteropolymer that contain NF-L or alpha-internexin plus NF-M or NF-H. Peripherin and vimentin may incorporate into neurofilaments along with these proteins. The NF-H and NF-M proteins have lengthy C-terminal tail domains that appear to control the spacing between neighboring filaments, generating aligned arrays with a fairly uniform interfilament spacing as seen in axons.

Growth

Antibody stain against Neurofilament (green) and Ki 67 (red) in a Mouse embryo 12.5 days after fertilization. The cells expressing neurofilaments are in the dorsal root ganglions shown in green while proliferating cells are in the ventricular zone in the neural tube and colored red.

During axonal growth, new neurofilament subunits are incorporated all along the axon in a dynamic process that involves the addition of subunits along the filament length, as well as the addition of subunits at the filament ends.

After an axon has grown and connected with its target cell, the diameter of the axon may increase as much as fivefold.

Neurofilaments are able to determine the diameter of dendrites and axons because their polarity causes them to repel each other.

The level of neurofilament gene expression seems to directly control axonal diameter, which in turn controls how fast electrical signals travel down the axon.[1]

Mutant mice with neurofilament abnormalies have phenotypes resembling amyotrophic lateral sclerosis.[2]

Use in diagnostic pathology

Micrograph of white matter (bottom of image) and the anterior horn of the spinal cord showing motor neurons with central chromatolysis. Neurofilament immunostain.

Neurofilament, NF, immunostaining is common in diagnostic neuropathology. It is useful for differentiating neurons (positive for NF) from glia (negative for NF).

See also

References

  1. ^ Alberts, Bruce (2002). Molecular biology of the cell (4th ed.). New York: Garland Science. ISBN 0-8153-3218-1. http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4. 
  2. ^ Lalonde R, Strazielle C; Strazielle (2003). "Neurobehavioral characteristics of mice with modified intermediate filament genes". Rev Neurosci 14 (4): 369–85. doi:10.1515/REVNEURO.2003.14.4.369. PMID 14640321. 

Wikimedia Foundation. 2010.

Look at other dictionaries:

  • neurofilament — ● neurofilament nom masculin Filament contenu dans l axoplasme …   Encyclopédie Universelle

  • Neurofilament — Le neurofilament est le filament intermédiaire trouvé spécifiquement dans les neurones. Cette fibre très fine mesure de 9 à 10 nm de diamètre, généralement regroupée en faisceau, est l élément de soutien du neurone. (partiellement traduit… …   Wikipédia en Français

  • neurofilament — Member of the class of intermediate filaments found in axons of nerve cells. In vertebrates assembled from three distinct protein subunits (NF L 68 kD; NF M 160 kD; NF H 200 kD) These proteins, if introduced into fibroblasts, will incorporate… …   Dictionary of molecular biology

  • neurofilament — neu·ro·fil·a·ment (no͝or ə fĭlʹə mənt, nyo͝or ) n. Any of the long, fine threads that make up a neurofibril.   neu ro·fil a·menʹtous ( mĕnʹtəs) adj. * * * …   Universalium

  • neurofilament — noun A neurofibril …   Wiktionary

  • neurofilament — A class of intermediate filaments found in neurons. * * * neu·ro·fil·a·ment fil ə mənt n a microscopic filament of protein that is found in the cytoplasm of neurons and that with neurotubules makes up the structure of neurofibrils… …   Medical dictionary

  • NEFM — Neurofilament, medium polypeptide Identifiers Symbols NEFM; NEF3; NF M; NFM External IDs …   Wikipedia

  • NFM — neurofilament protein, medium polypeptide …   Medical dictionary

  • NFM — • neurofilament protein, medium polypeptide …   Dictionary of medical acronyms & abbreviations

  • NEFL — For the semi professional football league NEFL, see New England Football League. Neurofilament, light polypeptide Identifiers Symbols NEFL; CMT1F; CMT2E; FLJ53642; NF L; NF68; NFL …   Wikipedia