I have just uploaded our first paper to the BioRxiv preprint server:
“OPPOSING MICROTUBULE MOTORS CONTROL MOTILITY, MORPHOLOGY, AND CARGO SEGREGATION DURING ER-TO-GOLGI TRANSPORT.”
Anna K Brown, Sylvie D Hunt, David J Stephens
The paper is a follow up to our Journal of Cell Science paper from 2013 in which we showed similar outcomes for motors in the endosomal system.
This paper has been long in the making and was in fact our starting point for the project. Despite us thinking that this would prove a more tractable system (with a defined end-point for trafficking etc) the endosomal system provided a better model for this work. In this project we have also really been trying to find membrane anchors for dynein that direct ER-to-Golgi transport. I’ll admit that we held off on publishing early in the hope that we did and that we could incorporate these assays into that work. Unfortunately it didn’t work out that way. We also could have published this some time ago before Anna (first author) left for maternity leave. I retained the hope of extending the study through other work even while she was away. This didn’t happen (but we still have hopes). We left these data out of Sylvie’s paper for clarity. That paper remained entirely focussed on the endosomal network.So now, we have decided to publish as a follow-up to Sylvie’s paper on sorting nexins and motors from last year, we had to choose what to do. This in our view did not have the necessary detail (“mechanistic insight”??) for somewhere like Molecular Biology of the Cell or Journal of Cell Science. This choice coincided with the opening of BioRxiv as a preprint server for Biology.
[Declaration: I (David) am an “Affiliate” of BioRxiv]
This seemed like a very good option for this work to get it in the public domain ASAP. We will also submit this to a journal for full peer review as I believe that this remains an important part of the process. As such posting on BioRxiv is not the end point on this journey just an extra step for us that makes our data (and interpretation) freely available to all immediately. We don’t have to wait for peer review, revision, formatting and hosting. I cannot see that as anything but a good thing. The preprint has a DOI so can be cited and easily referred to. We can now decide where to submit this for full peer review. Many journals already allow posting (including EMBO and PLOS) and likely others will soon change their editorial policies to follow suit. Some won’t and that is their prerogative. Would we still send our future work to one of the journals that does not allow BioRxiv posting first? Yes, if we thought it was the most appropriate place, we certainly would.
Our funder for this work (the UK Medical Research Council or MRC) mandates open access and I think BioRxiv is a good part of this process. I also chose the CC-BY license option as the most liberal in terms of re-use, data mining etc. This is also consistent with our funder policy.
For further info on BioRxiv I recommend you take a look. The common questions are readily answered on the BioRxiv website.
Alfonso Martinez-Arias has written on his blog on why he supports the preprint server system and I see no point in reiterating comments that I agree with! I strongly recommend that you read this if you are still wondering whether this is a good idea or not.
I evaluated the following article for F1000Prime. The original evaluation is published at http://f1000.com/prime/717995214 . This evaluation has a DOI of 10.3410/f.717995214.793476314
Structural basis for kinesin-1:cargo recognition.
S Pernigo, A Lamprecht, RA Steiner and MP Dodding (2013)
This paper provides a basis to modulate cargo-motor interactions with a high degree of selectivity. The paper from Dodding and colleagues describes a crystal structure of the tetratricopeptide (TPR)-repeat domain of kinesin light chain (KLC) 2 in association with cargo. Conventional kinesin is a heterotetramer consisting of two each of heavy chain and light chain subunits. Cargo binds to the light chains by virtue of a “tryptophan-acidic motif”.
The new structure was obtained by engineering an in-frame fusion of the cargo, in this case SKIP (SifA-kinesin interacting protein) from the pathogen Salmonella, to the light chain. The structure reveals a number of intriguing features, including an apparent conformational shift in the TPR domain upon cargo binding to enclose the critical tryptophan determinant. This same binding site is also used by a very different cargo, calsyntenin, indicating that this site could serve as a contact site for all kinesin-interacting cargo that displays this tryptophan-acidic motif.
Furthermore, the authors propose a model in which those cargoes, including SKIP, which present two canonical KLC binding motifs might act to bridge the two light chains found in the kinesin tetramer. Such a model immediately proposes a means by which high-affinity cargo binding could transmit a large conformational change through the helical domain of the heavy chain. Further work to determine the validity of this model is clearly a high priority.
I evaluated the following article for F1000 Prime.
The Microtubule-Binding Protein Ensconsin Is an Essential Cofactor of Kinesin-1.
Barlan K, Lu W, Gelfand VI.
Curr Biol 2013 PMID: 23394833 DOI: 10.1016/j.cub.2013.01.008
This paper defines the microtubule binding protein ensconsin as an obligate co-factor for kinesin-1 drive in motility in Drosophila. In a series of elegant experiments, the authors show that ensconsin is not required for the recruitment of kinesin to membranes but is in some way involved in activating the motor. Ensconsin does not seem to affect the amount of membrane-bound kinesin in cells so the authors sought to define its role in motor activation. Kinesin-1 normally exists in an auto-inhibited confirmation in cells. In a key experiment the authors showed that removal of this auto-inhibition within the kinesin-1 motor by mutation eliminates the requirement for ensoconsin in vivo. These data suggest a model in which ensconsin acts to relieve the auto-inhibition. An important point is that this function of ensconsin did not require its own microtubule binding activity. The authors postulate that spatial restriction of ensconsin to microtubules acts to refine the spatial activation of kinesin-1, adding to the diversity of mechanisms that control the spatial and temporal organization of microtubule motor activation.