Neurofilament

Neurofilaments are the 10 nanometer (10nm) or intermediate filaments found specifically in neurons. The subunits of neurofilaments are related structurally to the 10nm or intermediate filaments of other tissues such as the keratin subunits, which make 10nm filaments expressed specifically in epithelia.

Class IV: NF-L, NF-M and NF-H
The family of proteins making intermediate filaments is divided into 5 major classes, the keratins forming the classes I and II. The neurofilament subunits occupy the class IV family of intermediate filaments, and was originally thought to contain only three proteins named NF-L, NF-M and NF-H.

These names come from 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. Neurofilaments are found in vertebrate neurons in especially high concentrations along the axons, where they appear to regulate axonal diameter.

In the adult mammal neurofilament subunit proteins coassemble in vivo, forming a heteropolymer that contain NF-L plus NF-M or NF-H. 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.

Class IV: Other
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.

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.

Class III
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.

Growth
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 repulsive. This is because their purpose is to set the diameter of dendrites and axons. They do this by repelling each other because of their polarity and move away from 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.