Writing and Reading the Tubulin Code

Ian Yu,Christopher P. Garnham,Antonina Roll-Mecak

doi:10.1074/jbc.r115.637447

Abstract

Microtubules give rise to intracellular structures with diverse morphologies and dynamics that are crucial for cell division, motility, and differentiation. They are decorated with abundant and chemically diverse posttranslational modifications that modulate their stability and interactions with cellular regulators. These modifications are important for the biogenesis and maintenance of complex microtubule arrays such as those found in spindles, cilia, neuronal processes, and platelets. Here we discuss the nature and subcellular distribution of these posttranslational marks whose patterns have been proposed to constitute a tubulin code that is interpreted by cellular effectors. We review the enzymes responsible for writing the tubulin code, explore their functional consequences, and identify outstanding challenges in deciphering the tubulin code.

Highlights

Microtubules give rise to intracellular structures with diverse morphologies and dynamics that are crucial for cell division, motility, and differentiation
They possess two seemingly contradictory properties; they are highly dynamic, exhibiting rapid growth and shrinkage of their ends [1], but are very rigid, with persistence lengths on the order of cellular dimensions [2]. This duality is thought to underlie the versatile architectures of microtubule networks in cells (Fig. 1) and is tuned by a myriad of cellular effectors. These fall into two categories: effectors that bind to the microtubule and alter its properties non-covalently (motors and microtubule-associated proteins (MAPs))2 and effectors that chemically modify the tubulin subunits
The field has made tremendous progress in recent decades identifying a compendium of microtubule-interacting proteins and understanding their interplay and regulation in the cell, we are just starting to unravel the basic mechanisms used by cells to chemically modify microtubules, despite the fact that tubulin posttranslational modifications have been known for over 40 years

Summary

Writing and Reading the Tubulin Code*

The complex microtubule modification patterns observed in cells are a function of the tissue distribution, developmental regulation, and biochemical properties of tubulin posttranslational modification enzymes (i.e. substrate specificity and kinetic parameters) in addition to the tissue-specific enrichment of certain tubulin isoforms. In addition to these first order factors, pre-existing modifications and their patterns may influence the further addition and removal of modifications. An understanding of the differential kinetic parameters of TTLL family members as well as other classes of tubulin modification enzymes is likely to illuminate how their molecular properties generate complex temporal and spatial modification patterns

Reading the Tubulin Code

How Does the Cell Interpret the Tubulin Code?