Possible involvement of ubiquitination in neurofilament degradation.
Ubiquitinated proteins are components of intraneuronal inclusions found in several degenerative diseases. Immunohistochemical studies of neurofilament accumulations in Lewy bodies suggest their possible ubiquitination. We investigated in the present work the presence and the nature of ubiquitin epitopes in purified neurofilament preparations from spinal cord. Ubiquitin antibodies consistently label the medium molecular weight neurofilament subunit, and to a lower extent the two other subunits of the neurofilament triplet. Ubiquitinated neurofilament epitopes are removed in vitro by incubation of neurofilaments with a deubiquitinase purified from nervous tissues. Studies of neurofilament degradation in vitro revealed that addition of ATP and exogenous ubiquitin stimulates the proteolysis of neurofilament by crude soluble fractions from nervous tissues. These observations favor the hypothesis of a physiological function of ubiquitin-associated pathways in degradation of neurofilaments in situ.
Gou
J P
JP
U298 INSERM, CHRU, Angers, France.
Leterrier
J F
JF
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D002417:Cattle; D007158:Immunologic Techniques; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism*; D010766:Phosphorylation; D013869:Thiolester Hydrolases / Q000378:metabolism; D043222:Ubiquitin Thiolesterase; D014452:Ubiquitins / Q000378:metabolism*
D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D014452:Ubiquitins; D000255:Adenosine Triphosphate; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase