Commentary and Perspective (Invited)
The third Japan-U.S. symposium on motor proteins and associated single-molecule biophysics
2023 年 20 巻 4 号 論文ID: e200037
詳細
2023 年 20 巻 4 号 論文ID: e200037
The third Japan-U.S. symposium on motor proteins and associated single-molecule biophysics will be held on 15 November 2023, during the 61st Annual Meeting of the Biophysical Society of Japan. This is a series of motor protein symposia, starting in 2021 [1,2], that will bring together researchers from Japan and the U.S.-two leading countries in the field- to foster the exchange of ideas and promote cutting-edge collaborative research. With a lineup of renowned experts in the field, this symposium provides an exceptional opportunity to present the latest advances in our understanding of motor protein movement and regulation.
This year’s symposium will focus on microtubule-based motility (Figure 1), where a number of new perspectives on the research topic have recently emerged. Microtubules and its associated motors provide driving forces for various types of movement in eukaryotic cells [3], such as chromosome segregation during cell division, morphological changes of developing cells, and intracellular transport of vesicles, organelles and viruses. The symposium will begin with the application of microtubule-based motility as a computer. The movement of microtubules driven by motors has long been used as a method to measure motor activity [4,5]. Later, with the discovery of the property that crowded microtubules can form groups and show peculiar patterns when sliding on a surface [6], this phenomenon has attracted much attention in terms of nonequilibrium statistical mechanics, a discipline of physics that studies the motion patterns of aggregated self-moving objects [7]. In this context, the Kakugo lab has developed a technique to manipulate the formation of microtubule swarms using light [8], and has made remarkable achievements in controlling the collective motion of microtubules. As a graduate student in the Kakugo lab, Mr. Yiming Gong (Kyoto University) will give a talk on the development of a method to use the swarming of microtubules as a computer. His computational system also revealed a new aspect of microtubule swarming.
Microtubule-based motility. In eukaryotic cells, many cargoes, including mitochondria, Golgi and endoplasmic vesicles, and viral particles, are transported along microtubules by kinesin and dynein motors. This symposium will dissect this motility from various aspects, such as its kinetics, role in the cell, regulatory system, and application.
The symposium will then turn to the molecular properties and regulatory mechanisms of motors. The microtubule cytoskeleton extends throughout the cytoplasm in eukaryotic cells, and vesicles are transported along the cytoskeletal network by the motors: kinesins and cytoplasmic dynein. While kinesins, which are mainly responsible for movement toward the plus end of microtubules, are subdivided into 45 species in humans [9], only one type of cytoplasmic dynein is responsible for movement toward the minus end in animal cytoplasm [10]. During vesicle transport in the cytoplasm, both kinesin and dynein are often found associated with the same vesicle [11]. Since the discovery that mammalian cytoplasmic dynein can exert a mechanical force comparable to that of kinesin when it forms a complex with dynactin and the adaptor protein Bicaudal-D2 [12], how kinesin and dynein regulate their activities to determine the direction of vesicular transport has become a major topic of research. Dr. William Hancock (Pennsylvania State University) has previously characterized the kinetics of kinesin movement and microtubule polymerization using single molecule measurements [13,14]. In this talk, he will describe the properties of three major kinesins, kinesin-1, 2, and 3, when they move in competition with the cytoplasmic dynein complex, and report how their kinetics are altered by the presence of the dynein complex [15]. Ms. Merve Aslan (University of California, Berkeley) will report on the regulatory mechanisms of kinesin and dynein in mitochondrial transport. She revealed the molecular basis of how the Miro1/TRAK adaptor proteins, which connect the motors and mitochondria, control and enable efficient and precise transport of mitochondria [16]. These talks will deepen our understanding of how the two opposing motors are controlled to provide site-specific transport.
The agenda of the symposium then gradually shifts to the role of motors in the cell. In plant cells, the shape of the microtubule cytoskeletal network is completely different from that in animal cells, and cytoplasmic dynein is absent, resulting in many kinesins of the same type having different properties from those in animal cells. Dr. Moe Yamada (Nagoya University) has been elucidating the properties of plant kinesins by taking advantage of the relative ease of genetic manipulation of moss plants [17–19]. In this symposium, she will talk about the interesting properties of the newly elucidated kinesin 12-II [20]. During plant cell division, the cell plate is formed by the delivery of Golgi and endosomal vesicles to the phragmoplast midzone. She reports that kinesin 12-II is responsible for this delivery and the functional commonality of the motor across species.
Returning to phenomena in animal cells, Dr. Greg Smith will report on his surprising discovery in the transport of alphaherpesviruses in neurons. The viruses recruit microtubule motors to infect neurons in a two-step process: the dynein complex-driven long-distance transport to the centrosome and the kinesin-1-driven transport from the centrosome to the nucleus. His team showed that the kinesin used for the latter step is not recruited from the cytoplasm during transport, but rather is incorporated and assimilated into the viral particle in a previously infected cell [21]. In his talk, he will also explain how a viral effector protein spatially and temporally regulates the assimilated kinesin motor to promote rapid intracellular trafficking of capsids to the nucleus, switching from long-distance dynein-driven transport [22].
Finally, Dr. Kumiko Hayashi, one of the organizers of this symposium, will give a talk on methods to measure the number of motor molecules operating during vesicular transport. It is well known that vesicles have many motor molecules bound to them, and the number of the attached kinesin and dynein molecules has a critical effect on the direction of movement and the force exerted, as in the mitochondrial transport described in Ms. Aslan’s talk. Due to the limited resolution of light microscopy, it has not been possible to visualize the number of motor molecules bound to each vesicle during transport. Dr. Hayashi developed a fluctuation-theorem based method to estimate this number [23]. Using this method, her team revealed the relationship between synaptic patterns in C. elegans motor neurons and the number of molecules of KIF1A, a kinesin that transports nerve vesicles [24]. She will discuss further applications of this method in her talk [25].
With this series of cutting-edge talks, this symposium will cover a wide range of topics from molecular activities of motors to intracellular functions and their applications. We expect that this symposium will promote exchanges between researchers in Japan and the U.S., and further advance research in this field.
