The Fission Yeast TACC Protein Mia1p Stabilizes Microtubule Arrays by Length-Independent Crosslinking

SummaryMicrotubule (MT) arrays are mechanistic effectors of polarity specification and cell division. Linear bundles in which MTs are bridged laterally 1 and 2 are dynamically assembled in systems ranging from differentiated metazoan cells to fungi in a process that remains poorly understood. Often, bundled MTs slide with respect to each other via molecular motors 3 and 4. In interphase cells of the fission yeast Schizosaccharomyces pombe, MT nucleation frequently occurs at preexisting arrays 5 and 6. As the nascent MT lengthens, stable antiparallel MT overlaps are thought to form through competition between motion of the minus-end-directed kinesin Klp2p [4] and braking force exerted by the accumulating lateral crosslinker Ase1p 7, 8 and 9. Here we show that Mia1p/Alp7p, a transforming acidic coiled-coil (TACC) protein 10 and 11, functions as a length-independent MT crosslinker. In cells lacking Mia1p MT-bundling activity, linear arrays frequently disassemble, accompanied by a marked increase in Ase1p off rate and erratic motion of sliding MTs. We propose that the combined action of lateral length-dependent (Ase1p) and terminal length-independent (Mia1p) crosslinkers is crucial for robust assembly and stability of linear MT arrays. Such use of qualitatively distinct crosslinking mechanisms in tandem may point to a general design principle in the engineering of stable cytoskeletal assemblies.