Discovery of Auto-regulation Mechanism of Motor Protein “Dynein”, Cargo Transporter in Cell

- Paving the way to understanding the control mechanism of intracellular transport -

October 15, 2014

Abstract

The auto-regulation mechanism of motor protein “dynein” has been discovered by a research group led by Researcher Takayuki Torisawa and Senior Researcher Ken’ya Furuta of the Advanced ICT Research Institute, National Institute of Information and Communications Technology (NICT) and Professor Yoko Y. Toyoshima of the Graduate School of Arts and Sciences, the University of Tokyo. The group has revealed that the motility of dynein is autoinhibited in the absence of cargo. This mechanism provides a fundamental layer of dynein regulation in the cell that supports higher layers of regulation involving various dynein regulators. This mechanism paves the way to understanding the control mechanism of the intracellular transport and may offer new targets in the treatment against virus diseases.

The achievements were published online in Nature Cell Biology on 28 September 2014.

Achievements

Two-state model of dynein

- In the absence of cargo, a motor protein dynein suppresses its own motor activity.

- In the inhibited state, dynein assumes a characteristic conformation in which two dynein motor heads are stacked together.

- The autoinhibition will provide a fundamental layer of dynein regulation to strictly control the transport in the cell.

Future Prospects

- The mechanism paves the way to understanding the control mechanism of the intracellular transport as an autonomous and delivered control system.

- It could offer new targets in the treatment against viral infection diseases.

Journal: Nature Cell Biology, DOI: 10.1038/ncb3048
URL: http://www.nature.com/ncb/journal/vaop/ncurrent/full/ncb3048.html
Title: Autoinhibition and cooperative activation mechanisms of cytoplasmic dynein

Author: Takayuki Torisawa, Muneyoshi Ichikawa, Akane Furuta, Kei Saito, Kazuhiro Oiwa, Hiroaki Kojima, Yoko Y. Toyoshima, and Ken’ya Furuta

Figure 1 Two-state model of dynein

- Figure 1 shows a schematic representation of two-state model of dynein with corresponding electron micrographs. Each dynein molecule switches stochastically between the two conformations.

Figure 2 Schematics and kymographs depicting the movement of dynein

- Figure 2(a) shows a schematic representation of the single-molecule tracking assay depicting a microtubule immobilized on the glass surface and dynein molecules moving along it.

- Figure 2(b) shows a kymograph depicting the movement of single cytoplasmic dynein molecules along a microtubule in the presence of 1 mM ATP. It shows bidirectional, diffusive movement along microtubules.

- Figure 2(c) shows a schematic representation of multiple-dynein complexes.

- Figure 2(d) shows that multiple-dynein complexes can drive directed transport.

- We have succeeded the reconstitution of collective transport that was driven by multiple-dynein complexes assembled on DNA scaffolds.

Technical Contact

Ken’ya Furuta
Bio ICT laboratory
Advanced ICT Research Institute
Tel: +81-78-969-2214
E-mail:

Media Contact

Sachiko Hirota
Public Relations Department
Tel: +81-42-327-6923
Fax: +81-42-327-7587
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Discovery of Auto-regulation Mechanism of Motor Protein “Dynein”, Cargo Transporter in Cell

Technical Contact

Media Contact

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