Proteolytic degradation of microtubule associated protein tau by thrombin.
Deposits in the brain of beta-amyloid and tau proteins constitute the two major characteristics of Alzheimer's disease. It is unknown how the deposits are formed, but several studies have suggested that proteases might play a crucial role. Consequently, the search for proteases responsible for processing tau and amyloid precursor protein has become relevant. Here, the ability of thrombin to process tau in vitro is examined. Thrombin, which is found in blood but presumably also in the nervous system, cleaves tau and generates a stable 25 kDa fragment. Immunoblot and amino acid sequencing reveals that the fragment is derived from the C-terminal of tau, and a microtubule assembly assay shows that it has a reduced capacity to promote microtubule assembly compared with full length tau.
Olesen
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Division of Biostructural Chemistry, Arhus University, Denmark.
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D006868:Hydrolysis; D015151:Immunoblotting; D007700:Kinetics; D008870:Microtubules / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D013552:Swine; D013917:Thrombin / Q000378:metabolism*; D014404:Tubulin / Q000302:isolation & purification / Q000378:metabolism*; D016875:tau Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*
D010446:Peptide Fragments; D011994:Recombinant Proteins; D014404:Tubulin; D016875:tau Proteins; D013917:Thrombin