TACC3-ch-TOG track the growing tips of microtubules independently of clathrin and Aurora-A phosphorylation.

Cristina Gutiérrez-Caballero,Selena G Burgess,Richard Bayliss,Stephen J Royle

doi:10.1242/bio.201410843

Cristina Gutiérrez-Caballero, Selena G Burgess + Show 2 more

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https://doi.org/10.1242/bio.201410843

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Journal: Biology open	Publication Date: Jan 16, 2015
Citations: 85	License type: CC BY 3.0

Affiliation: University of Warwick, University of Leicester

Abstract

ABSTRACTThe interaction between TACC3 (transforming acidic coiled coil protein 3) and the microtubule polymerase ch-TOG (colonic, hepatic tumor overexpressed gene) is evolutionarily conserved. Loading of TACC3–ch-TOG onto mitotic spindle microtubules requires the phosphorylation of TACC3 by Aurora-A kinase and the subsequent interaction of TACC3 with clathrin to form a microtubule-binding surface. Recent work indicates that TACC3 can track the plus-ends of microtubules and modulate microtubule dynamics in non-dividing cells via its interaction with ch-TOG. Whether there is a pool of TACC3–ch-TOG that is independent of clathrin in human cells, and what is the function of this pool, are open questions. Here, we describe the molecular interaction between TACC3 and ch-TOG that permits TACC3 recruitment to the plus-ends of microtubules. This TACC3–ch-TOG pool is independent of EB1, EB3, Aurora-A phosphorylation and binding to clathrin. We also describe the distinct combinatorial subcellular pools of TACC3, ch-TOG and clathrin. TACC3 is often described as a centrosomal protein, but we show that there is no significant population of TACC3 at centrosomes. The delineation of distinct protein pools reveals a simplified view of how these proteins are organized and controlled by post-translational modification.

Highlights

Microtubules (MTs) are dynamic polymers of α/β-tubulin that are involved in numerous cellular processes, including intracellular transport, chromosome segregation and control of cell shape and migration
In interphase and mitotic cells, GFP-Transforming acidic coiled-coil protein 3 (TACC3) formed clear punctate structures that moved in a directed manner, suggesting that TACC3 could behave as a MT plus-end tracking protein (+TIP)
In this paper we have described how TACC3 and ch-TOG interact at the plusends of MTs in human cells in interphase or mitosis

Summary

Introduction

Microtubules (MTs) are dynamic polymers of α/β-tubulin that are involved in numerous cellular processes, including intracellular transport, chromosome segregation and control of cell shape and migration. MT plus-end tracking proteins (+TIPs) bind the plus-ends of MTs, typically during episodes of growth (Akhmanova and Steinmetz, 2010). An exception is ch-TOG/XMAP215 which contains no [ST]X[IL]P motifs (Jiang et al, 2012) and tracks MT plusends ahead of EB proteins (Maurer et al, 2014; Nakamura et al, 2012; Zanic et al, 2013). EB proteins bind growing ends of MTs, but do not select between plus- and minus-ends, whereas ch-TOG/XMAP215 only binds the plus-ends but does not distinguish between growing and shrinking ends (Maurer et al, 2014; Zanic et al, 2013)

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