We have a new paper out! You can access it here.
The work was mainly done by Cristina Gutiérrez Caballero, a post-doc in the lab. We had some help from Selena Burgess and Richard Bayliss at the University of Leicester, with whom we have an ongoing collaboration.
The paper in a nutshell
We found that TACC3 binds the plus-ends of microtubules via an interaction with ch-TOG. So TACC3 is a +TIP.
What is a +TIP?
This is a term used to describe proteins that bind to the plus-ends of microtubules. Microtubules are a major component of the cell’s cytoskeleton. They are polymers of alpha/beta-tubulin that grow and shrink, a feature known as dynamic instability. A microtubule has polarity, the fast growing end is known as the plus-end, and the slower growing end is referred to as the minus-end. There are many proteins that bind to the plus-end and these are termed +TIPs.
OK, so what are TACC3 and ch-TOG?
They are two proteins found on the mitotic spindle. TACC3 is an acronym for transforming acidic coiled-coil protein 3, and ch-TOG stands for colonic hepatic tumour overexpressed gene. As you can tell from the names they were discovered due to their altered expression in certain human cancers. TACC3 is a well-known substrate for Aurora A kinase, which is an enzyme that is often amplified in cancer. The ch-TOG protein is thought to be a microtubule polymerase, i.e. an enzyme that helps microtubules grow. In the paper, we describe how TACC3 and ch-TOG stick together at the microtubule end. TACC3 and ch-TOG are at the very end of the microtubule, they move ahead of other +TIPs like “end-binding proteins”, e.g. EB3.
What is the function of TACC3 as a +TIP?
We think that TACC3 is piggybacking on ch-TOG while it is acting as a polymerase, but any biological function or consequence of this piggybacking was difficult to detect. We couldn’t see any clear effect on microtubule dynamics when we removed or overexpressed TACC3. We did find that loss of TACC3 affects how cells migrate, but this is not likely to be due to a change in microtubule dynamics.
I thought TACC3 and ch-TOG were centrosomal proteins…
In the paper we look again at this and find that there are different pools of TACC3, ch-TOG and clathrin (alone and in combination) and describe how they reside in different places in the cell. Although ch-TOG is clearly at centrosomes, we don’t find TACC3 at centrosomes, although it is on microtubules that cluster near the centrosomes at the spindle pole. TACC3 is often described as a centrosomal protein in lots of other papers, but this is quite misleading.
We were on the cover – whatever that means in the digital age! We imaged a cell expressing tagged EB3 proteins, EB3 is another +TIP. We coloured consecutive frames different colours and the result looked pretty striking. Biology Open picked it as their cover, which we were really pleased about. Our paper is AOP at the moment and so hopefully they won’t change their mind by the time it appears in the next issue.
This is the second paper that we have deposited as a preprint at bioRxiv (not counting a third paper that we preprinted after it was accepted). I was keen to preprint this particular paper because we became aware that two other groups had similar results following a meeting last summer. Strangely, a week or so after preprinting and submitting to a journal, a paper from a completely different group appeared with a very similar finding! We’d been “scooped”. They had found that the Xenopus homologue of TACC3 was a +TIP in retinal neuronal cultures. The other group had clearly beaten us to it, having submitted their paper some time before our preprint. The reviewers of our paper complained that our data was no longer novel and our paper was rejected. This was annoying because there were lots of novel findings in our paper that weren’t in theirs (and vice versa). The reviewers did make some other constructive suggestions that we incorporated into the manuscript. We updated our preprint and then submitted to Biology Open. One advantage of the preprinting process is that the changes we made can be seen by all. Biology Open were great and took a decision based on our comments from the other journal and the changes we had made in response to them. Their decision to provisionally accept the paper was made in four days. Like our last experience publishing in Biology Open, it was very positive.
Gutiérrez-Caballero, C., Burgess, S.G., Bayliss, R. & Royle, S.J. (2015) TACC3-ch-TOG track the growing tips of microtubules independently of clathrin and Aurora-A phosphorylation. Biol. Open doi:10.1242/bio.201410843.
Nwagbara, B. U., Faris, A. E., Bearce, E. A., Erdogan, B., Ebbert, P. T., Evans, M. F., Rutherford, E. L., Enzenbacher, T. B. and Lowery, L. A. (2014) TACC3 is a microtubule plus end-tracking protein that promotes axon elongation and also regulates microtubule plus end dynamics in multiple embryonic cell types. Mol. Biol. Cell 25, 3350-3362.
The post title is taken from the last track on The Orb’s U.F.Orb album.