<i>De novo</i> mutations in KIF1A-associated neuronal disorder (KAND) dominant-negatively inhibit motor activity and axonal transport of synaptic vesicle precursors

Anazawa, Yuzu; Kita, Tomoki; Hayashi, Kumiko

doi:10.1101/2021.07.22.453457

Cited by 3 publications

(2 citation statements)

References 71 publications

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“…Interpretation of return-level plots based on the force-velocity relationship is a promising tool for future research regarding neuronal diseases, particularly, KIF1A-associated neurological disorders 41, 42 . KIF1A is a type of kinesin-transporting synaptic vesicle precursor cargo, and the force and velocity of pathogenic mutant KIF1A was reported to be impaired 41, 42 . Because in vivo force measurement is difficult, the estimation of physical properties using EVA can be helpful for understanding the in vivo behavior of motor proteins.…”

Section: Discussionmentioning

confidence: 99%

Extreme-Value Analysis of Intracellular Cargo Transport by Motor Proteins

Naoi

Kagawa

Nagino

et al. 2021

Preprint

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In the long axon of a neuron, cargo transport between the cell body and terminal synaptic region are mainly supported by the motor proteins kinesin and dynein, which are nano-sized drivers. Synaptic materials packed as cargos are anterogradely transported to the synaptic region by kinesin, whereas materials accumulated at the axon terminals are returned to the cell body by dynein. Extreme value analysis, typically used for disaster prevention in our society, was applied to analyze the velocity of kinesin and dynein nanosized drivers to disclose their physical properties in living cells.

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Section: Discussionmentioning

confidence: 99%

Extreme-Value Analysis of Intracellular Cargo Transport by Motor Proteins

Naoi

Kagawa

Nagino

et al. 2021

Preprint

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“…From the Japanese perspective, recent studies from three laboratories have been introduced. Dr. Ryohei Kobayashi from the Hiroyuki Noji lab [8] discusses the single-molecule experiment on IF 1 , a regulatory protein of mitochondrial ATP synthase [9]; Dr. Jakia Jannet Keya from the Ryota Iino lab [10] talks about engineering hybrid kinesin with a synthetic linker [11]; and Dr. Shinsuke Niwa, sharing the talk with Dr. Kyoko Chiba from the Shinsuke Niwa lab [12], provides topics on genetics using C. elegans and single-molecule experiments with several types of kinesin [13,14]. Dr. Kumiko Hayashi [15], who is a member of both the Biophysical Society [16] and the Biophsyical Society of Japan [1], is the moderator and overall host of the joint symposium, promoting debates from an interdisciplinary point of view.…”

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Japan-US symposium on cytoskeletal motor proteins and their associated proteins

Hayashi

Niwa

2021

BIOPHYSICS

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Over the last decade, the Biophysical Society of Japan [1] has encouraged holding exchange symposiums among overseas countries. So far, such symposiums were held with Asian countries mainly because in-person meetings were preconditions and Asian countries are geographically close to Japan. Under the pandemic situation, this precondition can be released by the possibility of virtual meetings. It is easier for us to attend international conferences online. Considering this as a merit of the pandemic situation, this time, for the 59 th Annual Meeting of the Biophysical Society of Japan, we plan to conduct a joint virtual symposium between Japan and the USA. We would like to state that the annual meeting was first thought to be held in person in Sendai, in 2021, commemorating the 10 th anniversary of the Great East Japan Earthquake. Sendai was one of the areas affected by the disaster. The meeting will be held as a symbol of the recovery of our society from the earthquake and COVID-19 pandemic.In the illustration of a cell for the webpage of the annual meeting (Fig. 1), one can see myosin fibers pulling actin filaments together, kinesin and dynein walk along microtubules transporting mitochondria and endosomes, and F o F 1 -ATP synthase rotates synthesizing ATP molecules inside the mitochondrion. Studies on these motor proteins are topics of the symposium. Speakers in this symposium are recognized internationally as experts in the field of motor proteins and their associated proteins. The symposium topics include multidisciplinary applications of genetics, bio-engineering, bio-chemistry, medical science, and physics of motor proteins, which will give us new insights into the motor proteins, as well as novel applications of existing single-molecule techniques.We have invited three speakers from the United States. Dr. Zev Bryant (Stanford University) will talk about engineering biomolecular motors. He describes the work of his group and their findings by saying "Molecular motors lie at the heart of biological processes ranging from DNA replication to cell migration. We use single-molecule tracking and manipulation to characterize the structural dynamics of these nanoscale assemblies, and further challenge our understanding by designing and testing structural variants with novel properties that expand the functional range of known biomolecular machines. In the process, we are developing an engineering capacity for molecular motors with tunable and dynamically controllable physical properties, providing a toolkit for precise perturbations of mechanical functions in vitro and in living cells." See details of the Bryant lab [2] and a recent publication [3].Dr. Erika Holzbaur (University of Pennsylvania) will talk about deciphering the function of activating adaptors in the motor-driven transport of mitochondria and autophagosomes. She summarizes the work of her group by saying "The axons of neurons are maintained by the active transport of organelles along the microtubule cytoskeleton, driven by the molecular motors cytopl...

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Intracellular force comparison of pathogenic KIF1A, KIF5, and dynein by fluctuation analysis

Hayashi

Matsumoto

Naoi

et al. 2021

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In mammalian cells, there exist approximately 40 types of microtubule motor proteins that are assigned to specific cargo deliveries. For example, the kinesin-1 family motor KIF5 is the major motor responsible for anterograde mitochondrial transport, whereas the kinesin-3 family motor KIF1A is responsible for synaptic vesicle precursor transport. In contrast, cytoplasmic dynein is responsible for retrograde transport of nearly all cargos. The force and velocity of these microtubule motors have been investigated in in-vitro single-molecule experiments. In the present study, we compared the intracellular force and velocity of various types of motors in the mammalian neuronal axon obtained by non-invasive force measurement (fluctuation analysis) and extreme value analysis with those obtained by previous single-molecule experiments. As we found a high correlation between our results and the previous results, we next investigated synaptic vesicle precursor transport by hereditary spastic paraplegia-associated KIF1A variants (V8M, R350G, and A255V). KIF1A-V8M and KIF1A-A255V exhibited force and velocity impairment in mammalian neuronal axons, whereas the physical property of KIF1A-R350G was similar to that of the wild type. We believe that the development of new analytical techniques for investigating intracellular cargo transports is helpful to elucidate the molecular mechanism of KIF1A-associated neurological disorders.

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De novo mutations in KIF1A-associated neuronal disorder (KAND) dominant-negatively inhibit motor activity and axonal transport of synaptic vesicle precursors

Cited by 3 publications

References 71 publications

Extreme-Value Analysis of Intracellular Cargo Transport by Motor Proteins

Extreme-Value Analysis of Intracellular Cargo Transport by Motor Proteins

Japan-US symposium on cytoskeletal motor proteins and their associated proteins

Intracellular force comparison of pathogenic KIF1A, KIF5, and dynein by fluctuation analysis

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