Supramolecular Structure of Assembly of Neurofilaments

Neurofilaments are composed of three subunit proteins of high, medium and low molecular weights; NF-H, NF-M, NF-L. In vitro, these subunits are able to self assemble via highly charged side arms that radiate from a 10 nm diameter core. Only NF-L and NF-M have been seen in axons that are in development or that are regenerating themselves. Here we are looking at varying ratios of NF-L and NF-H protein subunits to determine the assembly saturation point at which NF-H is in too high of a concentration that it will no longer assemble with NF-L to make mature NF's. We have found with increasing amounts of NF-H to NF-L, fewer and fewer NF-H subunits spin down to assemble with NF-L. In vivo, an abnormal accumulation of neurofilaments is a hallmark of nerve damage in certain neurodegenerative diseases. The saturation point of assembly between NF-L, NF-M and between NF-L, NF-H can be used to build a reference point of tolerable levels of all three protein subunits in the myelinated axon.