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 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 carboxyl-terminal position of the .alpha. chain of tubulin, nor a carboxypeptidase-like activity. Pulse-chase experiments demonstrated that, in the reconstituted rat brain preparations, detyrosination occurs late in the transit of dimers through the microtubule. Dimer loss and detyrosination during treadmill metabolism in these systems are linked.