title: TACC3-ch-TOG track the growing tips of microtubules independently of clathrin and Aurora-A phosphorylation.
abstract: The 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.
authors.affiliation: Division of Biomedical Cell Biology, Warwick Medical School, Gibbet Hill Road, Coventry, CV4 7AL, UK.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gutiérrez-Caballero
authors.affiliation: Cancer Research UK Leicester Centre and Department of Biochemistry, University of Leicester, Leicester LE1 9HN, UK.
authors.forename: Selena G
authors.initials: SG
authors.lastname: Burgess
authors.affiliation: Cancer Research UK Leicester Centre and Department of Biochemistry, University of Leicester, Leicester LE1 9HN, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Bayliss
authors.affiliation: Division of Biomedical Cell Biology, Warwick Medical School, Gibbet Hill Road, Coventry, CV4 7AL, UK s.j.royle@warwick.ac.uk.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Royle
keywords: +TIP; Microtubule dynamics; TACC3; XMAP215; ch-TOG