POSSIBLE INVOLVEMENT OF UBIQUITINATION IN NEUROFILAMENT DEGRADATION

Ubiquitinated proteins are components of intraneuronal inclusions foun d in several degenerative diseases. Immunohistochemical studies of neu rofilament accumulations in Lewy bodies suggest their possible ubiquit ination. We investigated in the present work the presence and the natu re of ubiquitin epitopes in purified neurofilament preparations from s pinal cord. Ubiquitin antibodies consistently label the medium molecul ar weight neurofilament subunit, and to a lower extent the two other s ubunits of the neurofilament triplet. Ubiquitinated neurofilament epit opes are removed in vitro by incubation of neurofilaments with a deubi quitinase purified from nervous tissues. Studies of neurofilament degr adation in vitro revealed that addition of ATP and exogenous ubiquitin stimulates the proteolysis of neurofilament by crude soluble fraction s from nervous tissues. These observations favor the hypothesis of a p hysiological function of ubiquitine-associated pathways in degradation of neurofilaments in situ. (C) 1995 Academic Press, Inc.