Neurofilament assembly

Brownlees, J., Ackerley, S., Grierson, A. J. et al. Charcot-Marie-Tooth disease neurofilament mutations disrupt neurofilament assembly and axonal transport. Hum. Molec. Genet. 11 2837-2844, 2002. 

PC12 Rat pheochromocytoma (adrenal medullary tumor) Adrenergic neuron Tricresyl phosphate (organophosphate) Inhibition of neurofilament assembly and axonal growth... 

In the medium and large neurofilament chains, where there are numerous K-S-P phosphorylation sites in the tail domains, the effect of phosphorylation is quite different. It has no visible effect on the state of filament assembly. It does, however, appear to be particularly important in determining axonal diameter (and concomitant conduction velocity), as well as transport properties and association with other cytoskeletal components. Experimentally, numerous phosphorylation sites have been shown to exist in a wide variety of IF proteins. Many others have been proposed on the basis of sequence motifs consistent with sites of known kinases. It has also been shown that mutations in which phosphorylation sites have been changed (see, for example, S35A in keratin 19) lead to various pathologies, including malformations in the filament assembly. 

Intermediate filaments are assemblies of intermediate filament proteins that provide mechanical strength to animal cells. Intermediate filaments include keratins, desmin filaments, vimentin filaments, nuclear lamins, and neurofilaments. The diameter of these filaments (about 10 nm) is intermediate between the thin actin filaments (about 7 nm) and the thicker microtubules (about 25 nm). Networks of cytoplasmic intermediate filaments are found throughout the cytoplasm of most animal cells, with some concentration around the nucleus. The lamin proteins make a network of intermediate filaments, the nuclear lamina, that lies just inside the nuclear membrane. 

Self-assembled nanostructures of biopolymers play an important role in nature. For example, extracellular branched polysaccharides decorate bacterial surfaces and therewith mediate cell adhesion [11], aggrecans (protein-polysaccharide complexes) control mechanical stresses in synovial joints [12], whereas neurofilaments (neuron-specific protein assemblies) support the elongated cell shape and participate in the maintenance of the axonal caliber [13]. It is believed that these biological functions rest on the ability of bioassemblies to provide adequate responses to variations in the local environment. Therefore, a better understanding of the physical mechanisms that govern conformational rearrangements in (bio)nanostructures, is of key importance, not only for colloid and material sciences, but also for cell biology. 

---