The amount of neurofilaments aggregated in the cell body is controlled by their increased sensitivity to trypsin-like proteases.
Neurofilaments are synthesised and assembled in neuronal cell bodies, transported along axons and degraded at the synapse. However, in several pathological situations they aggregate in cell bodies or axons. To investigate their turnover when separated from their normal site of degradation, we used a previously described transgenic model characterised by perikaryal retention of neurofilaments, and compared the basic features of both neurofilament synthesis and degradation with that observed in normal mice. Despite the massive perikaryal aggregates, neurofilament transcript levels were found to be unchanged, whereas the total accumulation of neurofilament proteins was markedly reduced. Neurofilaments isolated from transgenic samples are more sensitive to both trypsin and alpha-chymotrypsin mediated proteolysis. Consistent with their greater in vitro sensitivity, trypsin immunolabeling of cell bodies was stronger in transgenic mice. These results show a novel mechanism to regulate the amount of neurofilaments when they abnormally aggregate.
Fasani
F
F
Laboratoire Neurobiologie and Transgenese, UPRES-EA 3143, INSERM, 4 rue Larrey, bâtiment Montéclair, CHU 49033 Angers CEDEX, France.
Bocquet
A
A
Robert
P
P
Peterson
A
A
Eyer
J
J
D000818:Animals; D001369:Axons / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D002918:Chymotrypsin / Q000737:chemistry*; D007382:Intermediate Filaments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D014357:Trypsin / Q000737:chemistry*
D016900:Neurofilament Proteins; D002918:Chymotrypsin; D014357:Trypsin