On the Mechanism of Turnover of the Carboxy-Terminal Tyrosine of the Alpha Chain of Tubulin

Abstract

The removal of tyrosine from the carboxyl terminus of the alpha chain of tubulin occurs predominantly from those tubulin dimers that are part of microtubules, and is dependent upon microtubular treadmill metabolism. A heretofore unrecognized factor is present in the high-speed supernatant fraction of rat brain homogenates that is required for detyrosination. This factor is neither tubulin:tyrosine ligase, the enzyme that catalyzes the addition of tyrosine to the carboxylterminal position of the alpha chain of tubulin, nor a carboxypeptidase-like activity. Pulse-chase experiments demonstrated that, in the reconstituted rat brain preparations, detyrosination takes place late in the transit of dimers through the microtubule and we suggest that dimer loss and detyrosination during treadmill metabolism in these systems are linked.