Posttranslational encoding of microtubule provides unique recognition patterns for associated proteins

Microtubules are key components of the eukaryotic cytoskeleton involved in vital functions in virtually every cell. Among the least explored molecular mechanisms to adapt microtubules to their diverse functions is the biochemical diversification of tubulin molecules by posttranslational modifications (PTMs) and differential gene expression, a concept known as the ‘tubulin code’. A key question remains whether the tubulin code has the potential to selectively control microtubule interactions of different microtubule-associated proteins (MAPs) to act as a specific signalling system. To answer this question, we used a medium-throughput in vitro approach to screen 46 proteins for their binding preferences to microtubules with altered PTM or isotype composition. We demonstrate that MAPs have unique sensitivities to PTMs. As a result, PTMs, or combinations of them, differentially attract or repulse individual MAPs to microtubules. Our findings offer mechanistic proof for a key hypothesis of the tubulin code – the capacity to selectively and differentially regulate MAP-microtubule interactions.