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Mechanosensitive ion channels
mini-symposium in Osaka
Date：Location：

June 7th, 2024 (Fri) 16：00～18：30
Osaka university graduate school of medicine,
Lecture room #C＜Agenda＞
Opening remarks
Dr. Masanori P. Takahashi

Lecture series
Dr. Kotaro Hirano, University of Shizuoka“The mechanosensitive ion channel PIEZO1 as a biophysical sensorof skeletal muscle stem cells”
Dr. Yun Lyna Luo, Western University“Mechano-electrical coupling in PIEZO channels”
Dr. Jerome Lacroix, Western University“Molecular mechanisms of PIEZO channel modulationby small molecules”
Discussion

All speakers with audience,Closing remarks(Facilitator Dr. Tomoya Kubota)
Dr. Tomoya Kubota

問い合わせ先：医学系研究科保健学専攻 久保田智哉 内線2587

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The mechanosensitive ion channel PIEZO1 as abiophysical sensor of skeletal muscle stem cells

Kotaro Hirano 先生
Assistant Professor
School of Pharmaceutical Sciences, University of Shizuoka
日時：2024年6月7日（金）16：00～16：40
場所：大阪大学医学部医学科講義棟 C講堂＜Abstract＞
Muscle satellite cells (MuSCs), myogenic stem cells inskeletal muscles, play an essential role in muscle
regeneration. However, the molecular mechanisms as tohow MuSCs sense physical stimuli remain to be elucidated.
Here we identified PIEZO1, a mechanosensitive Ca2+
channel that is activated by membrane tension, as a key
regulator of myofiber regeneration. Our results reveal thatPIEZO1 plays a role in MuSC division in a Rho-dependent
manner, suggesting that the mechanosensing machinery iscentral to the maintenance of skeletal muscle homeostasis.

＜Selected publications＞
Hirano, et. al., The mechanosensitive ion channel PIEZO1
promotes satellite cell function in muscle regeneration,
Life Science Alliance, 2023

問い合わせ先：医学系研究科保健学専攻 久保田智哉 内線2587

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Mechano-electrical coupling inPIEZO channels

Yun Lyna Luo 先生
Associate Professor
Biotechnology and Pharmaceutical Sciences,
Western University
日時：2024年6月7日（金）16：40～17：20
場所：大阪大学医学部医学科講義棟 C講堂
Mechanosensitive ion channels, PIEZO1 and PIEZO2, convert
mechanical forces into electrical signals in vertebrates. Using
atomistic and hybrid-resolution molecular dynamics techniques,
we simulated PIEZO1&2 gating motion in response to changes
in membrane curvature and physiological lateral tension. Toinvestigate whether multiple PIEZO channels may undergo
cooperative gating, we developed a super coarse-grained model
to simulate the spontaneous clustering of channels in a
submicron membrane patch.
Jiang, et. al., Structural and thermodynamic framework for PIEZO1 modulation
by small molecules, PNAS, 2023
Jiang, et. al., Crowding-induced opening of the mechanosensitive Piezo1
channel in silico. Commun. Biol. 2021
Botello-Smith, et al., A molecular Mechanism for the Chemical Activation of theMechanosensitive Piezo1 Channel, Nat. Commun., 2019

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問い合わせ先：医学系研究科保健学専攻 久保田智哉 内線2587

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Molecular mechanisms of PIEZO channel
modulation by small molecules

Jerome Lacroix 先生
Associate Professor
Department of Basic Medical Sciences,
Western University of Health Sciences, USA

日時：2024年6月7日（金）17：20～18：00
場所：大阪大学医学部医学科講義棟 C講堂
PIEZO1/2 ion channels constitute essential mechanotransducers
in vertebrates. Pharmacological modulation of PIEZO1 andPIEZO2 could offer many clinical benefits to treat a diversity ofailments including pain, cancer, hypertension, and wound healing.
My talk will focus on our efforts in identifying the binding siteand pharmacological mechanism of Yoda1, a synthetic small
molecule PIEZO1 activator, and how to harness this knowledge
for future structure-based drug discovery.
Structural and thermodynamic framework for PIEZO1 modulation by small molecules.
Jiang et al., PNAS, 2023
Yoda1's energetic footprint on Piezo1 channels and its modulation by voltage and temperature.
Wijerathne et al., PNAS, 2022
A mechanism for the activation of the mechanosensitive Piezo1 channel by the small molecule Yoda1.
Botello-Smith et. al., Nature Communications, 2019
Probing the gating mechanism of the mechanosensitive channel Piezo1 with the small molecule Yoda1.
Lacroix et. al., Nature Communications, 2018

保健学科国際交流センター共催
問い合わせ先：医学系研究科保健学専攻 久保田智哉 内線2587