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Today we have a meeting report from F1000 Member David Stephens, who is in the Department of Biochemistry at Bristol University. David went to the recent Biochemical Society/Wellcome Trust Focused Meeting on Cellular cytoskeletal motor proteins, held at the Wellcome Trust Genome Campus near Cambridge.

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For a fantastic summary of the state of the art of the molecular motors field, there was no better place to be than Cambridge, UK in late March 2011. This meeting, organized by Folma Buss and Jake Kendrick Jones, was sponsored by The Biochemical Society and the Wellcome Trust. It provided a short and intense snapshot of the myosin, kinesin and dynein fields, covering all experimental and theoretical approaches–from single molecule imaging through mathematical modelling to whole organism biology.

The opening session was launched with an outstanding talk from Kristen Verhey, in which she talked mainly about her recent paper on the role of the Ran GTPase and nuclear import factors in controlling trafficking to the primary cilium ^{10.1038/ncb2073}. The session continued with Volodya Gelfand highlighting one of the standout themes of much of the work presented at the meeting–bidirectional motility and reciprocal control of opposing motor activities. The fundamental point of this work to my mind was that suppression of one motor abolished bidirectional motility. In rescue-type experiments with synthetically constructed motors, Gelfand showed that any minus end motor was sufficient to restore bidirectional motility following suppression of dynein. This experiment shows that mechanical coupling of opposing motors is required to drive motility of peroxisomes in Drosophila S2 cells^{10.1083/jcb.200908075}. A key question of course is how generally applicable this is to other systems, notably those that are concerned with less discrete structures such as amorphous tubular membranes of the endoplasmic reticulum and endosomal systems. These two talks provided a great opening to the meeting and highlighted the diversity of experimental systems, cytoskeletal motors and regulatory mechanisms involved. The first session continued late into the night, maintaining its intensity into the next day.

There were many great talks at the meeting. I particularly enjoyed listening to Isabelle Vernos (Barcelona) on some new aspects of microtubule nucleation relating to the K-fibers that attach to kinetochores during mitosis, and Simon Bullock (LMB Cambridge) on dynein-dependent trafficking of mRNA particles during Drosophila embryogenesis, suggesting that in contrast to some previously published data, in this system at least, motor copy number can have a major impact on directional motility.

Andrew Carter (LMB Cambridge) described his elegant recently published structure of the dynein motor domain^{10.1126/science.1202393}; John Hammer (NIH) presented his elegant data concerning spine formation on Purkinje neurons^{10.1038/ncb2132} and definitely scooped the award for outstanding images; Viki Allan and I both discussed our own (largely unpublished) evidence for and against specific roles for each of the dynein light intermediate chain subunits as well as considerable further data (notably from Viki) concerning potential mechanisms of regulation and roles of these subunits in the context of the intact dynein motor. Our work highlights a key complexity in dynein biology–how does one motor associate with so many cellular targets? We are making inroads on this question and complementary approaches seem likely to reveal major insights in the not too distant future.

Other highlights included the eventual best-talk winner Mark Dodding (formerly of Michael Way’s lab at CRUK, now independent at Kings College London), detailing elegant work defining a kinesin-binding signature across the genome. His work provides yet another great example of the use of pathogens as tools to develop our understanding of complex cell biology systems. The poster prize was awarded to Lisa Bond, working on a PhD jointly between the labs of Folma Buss in Cambridge and Jim Sellers at NIH, whose work on myosin VI and optineurin in secretory vesicle fusion was published recently^{10.1091/mbc.E10-06-0553}. Justin Molloy (NIMR London), Rob Cross (Warwick), and Stefan Diez (Dresden) each presented intriguing data from in vitro reconstitution systems. A critical point from these experiments for me was that they illustrate how much can be obtained from looking at tractable in vitro systems as well as single molecule dynamics. A clear outcome from much of the in vivo and intact cell work presented at the meeting is that these data are cannot always be translated directly to more complex systems. Indeed, the complexities of in vitro systems themselves are highlighted by the important distinctions in observed behaviour (nicely demonstrated by Rob Cross’ lab) when studying a truly homologous system–i.e. yeast motors with yeast tubulin^{10.1074/jbc.C109.052159}. The final session, which was dominated by mathematical modelling, highlighted the need for careful biochemical measurement as well as a thorough understanding of the number of molecules and affinities of interactions in vivo. Only then can these vital parameters inform the development of such models.

The meeting provided throughout a wonderful balance–overseas and UK speakers, mechanistic biochemistry through cell biology to whole organism development, as well as a range of junior to senior speakers. In this regard the organizers deserve high praise. While encouraged by the Biochemical Society, social media is clearly yet to take off but still provided an opportunity for me at least to meet new colleagues working on similar problems (admittedly we would definitely have done so outside the twittersphere). As all good meetings should, I left Cambridge with as many questions as answers. The forthcoming volume of Biochemical Society Transactions 39(5) will include reviews written by invited speakers on topics relating to their presentations. This will be worth looking out for by those unable to make the meeting, as well as delegates themselves.

Prof. David Stephens, School of Biochemistry, University of Bristol.
david.stephens’at’bristol.ac.uk
@david_s_bris
https://www.bristol.ac.uk/biochemistry/stephens/index.html