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RNA-directed activation of cytoplasmic dynein-1 in reconstituted transport RNPs

Mark A McClintock, Carly I Dix, Christopher M Johnson, Stephen H McLaughlin, Rory J Maizels, Ha Thi Hoang, Simon L Bullock

Preprint posted on March 08, 2018 https://www.biorxiv.org/content/early/2018/03/08/273912

and

Recruitment of Two Dyneins to an mRNA-Dependent Bicaudal D Transport Complex

Thomas E. Sladewski, Neil Billington, M. Yusuf Ali, Carol S. Bookwalter, Hailong Lu, Elena B. Krementsova, Trina A. Schroer, Kathleen M. Trybus

Preprint posted on February 28, 2018 https://www.biorxiv.org/content/early/2018/02/28/273755

How come dynein runs faster and longer when loaded with an RNA cargo? New in vitro single-molecule assays and electron microscopy reveal molecular mechanisms

Selected by Dmitry Nashchekin

Summary

Cytoplasmic dynein-1 (dynein) is an essential motor complex for mRNA transport and localisation. Motor activity of dynein is regulated by cargo adaptor proteins1,2, but whether mRNA could influence the efficiency of dynein as well has remained unclear. These two preprints from the Bullock and Trybus labs show that mRNA could work as a scaffolding structure bringing together adaptor and motor proteins. Only when all components are in place is dynein switched on and able to work as a full power motor. These studies provide a new paradigm of how mRNA and probably other cargos could stimulate their own transport.

Key findings and bigger picture

The authors follow up on previous observations that the dynein/dynactin complex exists in an autoinhibitory state and requires adaptor proteins and cargos to be converted to a highly processive motor. With the help of a new single molecule RNA transport assay from the purified components (McClintock et al. and Sladewski, Billington, Ali et al.) paired with electron microscopy (Sladewski, Billington, Ali et al.), the authors are able to offer a new model for the regulation of dynein transport. They provide molecular mechanisms of how the presence of a localisation signal on mRNA could be converted, through adaptor proteins, to the activity of the motor. Interestingly, Sladewski et al. also show that the speed of the RNA transport could be regulated not only by the dynein activity per se but also by the number of motors attracted to the cargo. This observation fits very nicely with the recent structural studies showing that adaptor proteins make transport faster by recruiting two dyneins at the cargo3,4.

Open questions

It will be interesting to see whether other types of dynein cargos (e.g. vesicles) could influence transport in a similar way.

In the transport assay, authors were able to achieve only half of the normal dynein speed. It would be exciting to find out what were the missing components that could stimulate dynein even further.

Related research

  1. McKenney, R.J., W. Huynh, M.E. Tanenbaum, G. Bhabha, and R.D. Vale. 2014. Activation of cytoplasmic dynein motility by dynactin-cargo adapter complexes. Science. 345:337-341.
  2. Schlager, M.A., H.T. Hoang, L. Urnavicius, S.L. Bullock, and A.P. Carter. 2014. In vitro reconstitution of a highly processive recombinant human dynein complex. EMBO J. 33:1855-1868.
  3. Urnavicius, L., C.K. Lau, M.M. Elshenawy, E. Morales-Rios, C. Motz, A. Yildiz, and A.P. Carter. 2018. Cryo-EM shows how dynactin recruits two dyneins for faster movement. Nature. 554:202-
206.
  4. Grotjahn, D.A., S. Chowdhury, Y. Xu, R.J. McKenney, T.A. Schroer, and G.C. Lander. 2018. Cryo-electron tomography reveals that dynactin recruits a team of dyneins for processive motility. Nat Struct Mol Biol.

 

Posted on: 27th March 2018

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