Post-Translational Modification in Microtubule Arrays Exhibits Spatial Patterns that can act as a Signal to Tightly Localize Motor-Driven Cargo

Abstract

Microtubule (MT) “age” has been interpreted through nucleotide state, lattice defects, and post-translational modification (PTM) such as acetylation and detyrosination. All three cases have been recently shown to have functionally-important effects on the dynamics of MT arrays, which can present spatial and temporal heterogeneity. While mathematical models for MT array densities are well-established, we present equations describing MT age, defined here as the mean time since the MT's building blocks (tubulin) were polymerized from their soluble dimer state. These equations can recapitulate the observation that the oldest (most acetylated) tubulin in axons is near the middle of axons during neuronal development. Furthermore, PTMs influence motor kinetics up to approximately 3-fold for off-rates and velocities. Our simulations demonstrate that this relatively weak dependence of motor kinetics is sufficient to target motor cargo to a specific location along the array. This localization is tightly peaked in a way that magnifies the relatively small signal of PTM spatial heterogeneity. Thus, MT age can produce long-range spatial patterning without feedbacks or diffusing signals.