The slow component of axonal transport. Identification of major structural polypeptides of the axon and their generality among mammalian neurons.

Abstract

This study of the slow component of axonal transport was aimed at two problems: the specific identification of polypeptides transported into the axon from the cell body, and the identification of structural polypeptides of the axoplasm. The axonal transport paradigm was used to obtain radioactively labeled axonal polypeptides in the rat ventral motor neuron and the cat spinal ganglion sensory neuron.Comparison of the slow component polypeptides from these two sources using sodium dodecyl sulfate (SDS)-polyacrylamide electrophoresis revealed that they are identical. In both cases five polypeptides account for more than 75% of the total radioactivity present in the slow component. Two of these polypeptides have been tentatively identified as tubulin, the microtubule protein, on the basis of their molecular weights. The three remaining polypeptides with molecular weights of 212,000, 160,000, and 68,000 daltons are constitutive, and as such appear to be associated with a single structure which has been tentatively identified as the 10-nm neurofilament. The 212,000-dalton polypeptide was found to comigrate in SDS gels with the heavy chain of chick muscle myosin. The demonstration on SDS gels that the slow component is composed of a small number of polypeptides which have identical molecular weights in neurons from different mammalian species suggests that these polypeptides comprise fundamental structures of vertebrate neurons.

Posttranslational modification of a neurofilament protein during axoplasmic transport: implications for regional specialization of CNS axons

“…In addition, these 140,000-145,000 tool wt NFP forms exhibited properties during axoplasmic 156 THE JOURNAL OF CELL BIOLOGY. VOLUME 94,1982 transport that are characteristic of NFPs in several mammalian central axons (3,18,24,59,65). With the other NFPs and tubulin, the 140,000 tool wt NFPs composed the slowest of five major groups of transported proteins (24,59,64).…”

“…Pufffled mammalian neurofdaments contain at least three major protein species in the molecular weight classes 68,000-72,000, 140,000-170,000, and 200,000-220,000 (1,6,7,25,57). The association of these proteins in a single organelle was initially suggested by their movement within one phase of axoplasmic transport (-0.2 mm/d) (3,18). The view that these major protein species are physically associated with the neurofdament is supported by the demonstration that isolated neurofilaments were decorated by antibodies directed against each of these proteins (48,66).…”

Regional modulation of neurofilament organization by myelination in normal axons

“…In large neurons neurofilaments are the most abundant cytoskeletal organelles, and have been postulated to act as important intrinsic determinants of axonal caliber (Hoffman et al, 1987). Neurofilaments in vertebrates are composed of three related proteins with apparent molecular weights of 68, 150, 200 kDa (NF-L, NF-M, and NF-H, respectively) (Hoffman and Lasek, 1975;Liem et al, 1978;Geisler et al, 1983;Willard and Simon, 1983;Hirokawa et al, 1984;Schlaepfer, 1987). All three ofthese proteins share a central rod domain, but they differ in their C-terminal regions.…”

Antineurofilament antibody evaluation in neuropsychiatric systemic lupus erythematosus

“…Its components can be divided into 3 distinct classes: microfilaments, microtubules, and intermediate filaments. The neuronal cell intermediate filament or neurofilament is composed of 3 separate polypeptides of molecular weights 205, 160, and 70 kd (14,15). Studies indicating an increased incidence of antineurofilament antibodies (ANFA) in viral infections of the CNS (16) and in paraneoplastic neurologic disease (17,18), as well as recent work indicating an increased incidence of anticytoskeletal antibodies in connective tissue disease (19), have provided the primary focus of our study, which is to examine the occurrence and titer of ANFA in patients with NPSLE.…”

“…Western 14 patients with atherosclerotic unilateral stroke, 10 patients with idiopathic epilepsy, 6 patients undergoing lumbar or cervical myelogram for evaluation of suspected degenerative disc disease, and 22 normal control subjects selected from hospital personnel were assayed for ANFA. A "miscellaneous" group composed of 6 additional patients was included because of the association of their connective tissue disease with neuropsychiatric symptoms; of these, 1 had BehGet's disease, 4 had systemic vasculitis, and 1 had isolated CNS vasculitis.…”