糟谷豪

Go Kasuya

基本情報

所属: 自治医科大学医学部生理学講座　統合生理学部門講師

学位: 博士（理学）(東京大学)

研究者番号: 80845115
ORCID ID: https://orcid.org/0000-0003-1756-5764
J-GLOBAL ID: 201901003448115571
researchmap会員ID: B000352971

外部リンク: https://scholar.google.co.jp/citations?user=ZKiWyWgAAAAJ&hl=ja&oi=sra

研究キーワード

研究分野

経歴

2024年4月 - 現在

自治医科大学医学部生理学講座統合生理学部門講師
2019年4月 - 2024年3月

自治医科大学医学部生理学講座統合生理学部門助教
2018年4月 - 2019年3月

独立行政法人医薬品医療機器総合機構

学歴

- 2018年3月

東京大学大学院理学系研究科生物科学専攻博士課程

委員歴

2023年3月 - 現在

日本生理学会評議員

論文

Compound heterozygous variants of CACNA1H change channel properties and contribute to intractable epilepsy with myoclonic-atonic seizures

Ayumi Matsumoto, Go Kasuya, Suvd Tumurbaatar, Takuya Masuda, Kei Wakabayashi, Masako Kawada, Yasutomi Higashikuni, Kazuhiro Muramatsu, Koichi Nakajo, Hitoshi Osaka, Takayoshi Matsumura

Journal of Human Genetics 2025年11月22日査読有り筆頭著者
Extracellular salt bridge networks around S4 implicated in HCN channel gating and heart disease

Kaei Ryu, Go Kasuya, Koichi Nakajo

Proceedings of the National Academy of Sciences 122(37) 2025年9月11日

The hyperpolarization-activated cyclic nucleotide-gated (HCN) channel is a voltage-gated cation channel that plays a crucial role in regulating cellular excitability, especially in cardiac pacemaker cells and neurons. Its dysregulation is linked to heart diseases such as bradycardia and neurological disorders such as epilepsy, Parkinson’s disease, and neuropathic pain. Structural and functional studies have revealed that the S4 voltage sensor of the HCN channel moves downward during hyperpolarization. Recent structural studies of HCN channels have shown that the extracellular portion of the S4 segment is approximately three helical turns longer than that of voltage-gated K ⁺ (Kv) channels. However, whether this extended extracellular part of S4 plays a functional role in gating is still unknown. In this study, utilizing the available HCN4 channel structures, we examined the formation of salt bridges in the extracellular part of S4 with the S5 segment and the S1-S2 linker. Results from charge-swapped mutants and double cysteine mutants suggested that sequential, stepwise salt bridge formation involving the extracellular positively charged amino acids of S4 plays a role in the voltage-dependent gating of HCN channels. Furthermore, we applied voltage clamp fluorometry to confirm that the extracellular salt bridge network affects the S4 movement. This extracellular S4 portion includes disease-related arginine residues, R375 and R378. Our results suggest that disruption of salt bridge formation may perturb the smooth transition of S4 movement and cause HCN channel dysfunction.
Identification of KCNE6, a new member of the KCNE family of potassium channel auxiliary subunits

Go Kasuya, Buntaro Zempo, Yasuhiro Yamamoto, Kaei Ryu, Fumihito Ono, Koichi Nakajo

Communications Biology 2024年12月19日査読有り筆頭著者責任著者
Dual allosteric modulation of voltage and calcium sensitivities of the Slo1-LRRC channel complex

Daichi Yamanouchi, Go Kasuya, Koichi Nakajo, Yoshiaki Kise, Osamu Nureki

Molecular Cell 2023年11月査読有り筆頭著者責任著者
Optimized tight binding between the S1 segment and KCNE3 is required for the constitutively open nature of the KCNQ1-KCNE3 channel complex

Go Kasuya, Koichi Nakajo

eLife 2022年11月4日査読有り筆頭著者責任著者

もっとみる

MISC

Structural basis of lipid-mediated gating in a two-pore domain potassium channel

Fumiya K. Sano, Go Kasuya, Kohei Yamaguchi, Takehiro Suzuki, Daichi Yamanouchi, Kana M. Hashimoto, Masataka Inoue, Kazuhiro Sawada, Ryuichiro Ishitani, Kenjiro Yoshimura, Hisato Hirano, Yuzuru Itoh, Koichi Nakajo, Naoshi Dohmae, Yoshiaki Kise, Osamu Nureki

2025年11月12日

Abstract TOK1 is the first identified member of the K2P channel family and contains additional N- and C-terminal domains, displaying a configuration distinct from that of canonical K2P channels. Although recent advances in structural studies of K2P channels have elucidated their architectures, the structural basis of TOK1 has remained unknown, limiting our understanding of its unique configuration. Here, we present the cryo-electron microscopy (cryo-EM) structure of TOK1, unveiling its distinctive domain architecture. Furthermore, the structures of TOK1 in three distinct states provide mechanistic insights into its regulation through lipid binding and dissociation. Phosphorylation of TOK1 induces the formation of an additional lipid-binding site, leading to channel inactivation. Conversely, upon activation, the phospholipid dissociates, allowing ion permeation. Our comprehensive study, integrating cryo-EM structural analysis, molecular dynamics simulations, electrophysiological recordings, and mass spectrometry, elucidates the distinctive features of TOK1, an atypical K2P channel, and provides a framework for understanding lipid-mediated regulation within this family.
Modulation of potassium channels by transmembrane auxiliary subunits via voltage‐sensing domains

Koichi Nakajo, Go Kasuya

Physiological Reports 12(6) 2024年3月19日査読有り招待有り

Abstract Voltage‐gated K⁺ (K_V) and Ca²⁺‐activated K⁺ (K_Ca) channels are essential proteins for membrane repolarization in excitable cells. They also play important physiological roles in non‐excitable cells. Their diverse physiological functions are in part the result of their auxiliary subunits. Auxiliary subunits can alter the expression level, voltage dependence, activation/deactivation kinetics, and inactivation properties of the bound channel. K_V and K_Ca channels are activated by membrane depolarization through the voltage‐sensing domain (VSD), so modulation of K_V and K_Ca channels through the VSD is reasonable. Recent cryo‐EM structures of the K_V or K_Ca channel complex with auxiliary subunits are shedding light on how these subunits bind to and modulate the VSD. In this review, we will discuss four examples of auxiliary subunits that bind directly to the VSD of K_V or K_Ca channels: KCNQ1–KCNE3, Kv4‐DPP6, Slo1‐β4, and Slo1‐γ1. Interestingly, their binding sites are all different. We also present some examples of how functionally critical binding sites can be determined by introducing mutations. These structure‐guided approaches would be effective in understanding how VSD‐bound auxiliary subunits modulate ion channels.
Recent Advances in the Structural Biology of the Volume-Regulated Anion Channel LRRC8

Go Kasuya, Osamu Nureki

Frontiers in Pharmacology 13 2022年5月11日査読有り招待有り筆頭著者責任著者

Members of the leucine-rich repeat-containing 8 (LRRC8) protein family, composed of five LRRC8A-E isoforms, are pore-forming components of the volume-regulated anion channel (VRAC), which is activated by cell swelling and releases chloride ions (Cl⁻) or other osmolytes to counteract cell swelling. Although the LRRC8 protein family was identified as the molecular entity of VRAC only in 2014, due to recent advances in cryo-electron microscopy (cryo-EM), various LRRC8 structures, including homo-hexameric LRRC8A and LRRC8D structures, as well as inhibitor-bound and synthetic single-domain antibody-bound homo-hexameric LRRC8A structures, have been reported, thus extending our understanding of the molecular mechanisms of this protein family. In this review, we describe the important features of LRRC8 provided by these structures, particularly the overall architectures, and the suggested mechanisms underlying pore inhibition and allosteric modulation by targeting the intracellular leucine-rich repeat (LRR) domain.
ATP作動性チャネルP2X受容体における競合阻害機構の構造基盤

糟谷豪, 山浦利章, MA Xiao-Bo, 中村凌熙, 武本瑞貴, 南雲啓充, 田中英一, 堂前直, 中根崇智, YU Ye, 石谷隆一郎, 松崎修, 服部素之, 濡木理

日本生化学会大会(Web) 90th 2017年
Structural insights into divalent cation modulations and ligand specificity of ATP-gated P2X receptor channels

Yuichiro Fujiwara, Go Kasuya, Motoyuki Hattori, Osamu Nureki

Journal of Physiological Sciences 66(Supplement1) S66 2016年査読有り
1P034 H+/Ca2交換輸送体における対向輸送の分子基盤(01B. 蛋白質:構造機能相関,ポスター,日本生物物理学会年会第51回(2013年度))

53(supplement1-2) S111-S111 2013年