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Proteolysis of Microtubule‐Associated Protein 2 and Tubulin by Cathepsin D
Author(s) -
Johnson Gail V. W.,
Litersky Joel M.,
Whitaker John N.
Publication year - 1991
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1991.tb06354.x
Subject(s) - cathepsin d , cathepsin o , biochemistry , cathepsin , tubulin , cathepsin a , proteolysis , microtubule , chemistry , cathepsin l , cathepsin b , hydrolysis , cathepsin e , in vitro , in vivo , vacuole , enzyme , microbiology and biotechnology , biology , cytoplasm
Abstract : The in vitro degradation of microtubule‐associated protein 2 (MAP‐2) and tubulin by the lysosomal aspartyl endopeptidase cathepsin D was studied. MAP‐2 was very sensitive to cathepsin D‐induced hydrolysis in a relatively broad, acidic pH range (3.0–5.0). However, at a pH value of 5.5, cathepsin D‐mediated hydrolysis of MAP‐2 was significantly reduced and at pH 6.0 only a small amount of MAP‐2 was degraded at 60 min. Interestingly, the two electro‐phoretic forms of MAP‐2 showed different sensitivities to cathepsin D‐induced degradation, with MAP‐2b being significantly more resistant to hydrolysis than MAP‐2a. To our knowledge, this is the first clear demonstration that MAP‐2 is a substrate in vitro for cathepsin D. In contrast to MAP‐2, tubulin was relatively resistant to cathepsin D‐induced hydrolysis. At pH 3.5 and an enzyme‐to‐substrate ratio of 1: 20, only 35% of the tubulin was degraded by cathepsin D at 60 min. The cathepsin D‐mediated hydrolysis of tubulin was optimal only at pH 4.5. These results demonstrate that MAP‐2 and tubulin are unequally susceptible to degradation by cathepsin D. These data also imply a potential for rapid degradation of MAP‐2 in vivo by cathepsin D either in lysosomes or perhaps autophagic vacuoles of the neuron.