Possible roles of actomyosin and mechanosensitive channels in substrate rigidity sensing of cells

• Project/Area Number: 24247028
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biophysics
• Research Institution: Nagoya University
• Principal Investigator: SOKABE Masahiro 名古屋大学, 医学(系)研究科(研究院), 特任教授 (10093428)
• Co-Investigator(Kenkyū-buntansha): TATSUMI Hitoshi 金沢工業大学, バイオ・化学部・応用バイオ学科, 教授 (20171720) ; HAYAKAWA Kimihide 名古屋大学, 医学系研究科, 特任講師 (60467280)
• Co-Investigator(Renkei-kenkyūsha): KOBAYASHI Takeshi 名古屋大学, 医学系研究科, 講師 (40402565)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥43,680,000 (Direct Cost: ¥33,600,000、Indirect Cost: ¥10,080,000); Fiscal Year 2014: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000); Fiscal Year 2013: ¥15,470,000 (Direct Cost: ¥11,900,000、Indirect Cost: ¥3,570,000); Fiscal Year 2012: ¥14,690,000 (Direct Cost: ¥11,300,000、Indirect Cost: ¥3,390,000)
• Keywords: メカノセンシング / 足場 / 機械受容チャネル / 細胞骨格 / 接着斑 / 機械刺激受容チャネル

Outline of Final Research Achievements

Various cellular activities including cell migration, spreading, proliferation and differentiation are critically influenced by substrate rigidity. To sense substrate rigidity, cells apply traction forces to cell-substrate adhesions via actin stress fibers and measure mechanical responses of the substrate. Besides mechanosensitive (MS) adaptor proteins, MS channels are involved in the substrate rigidity sensing. MS channels located at or near focal adhesions convert the rigidity-dependent stress generated in stress fibers system into the level of cytoplasmic calcium ion concentration by locally altering their calcium ion permeability. Besides by external forces, cells spontaneously generate rigidity-dependent localized cytoplasmic calcium ion concentration increases, implicating MS channels as intrinsic force measurement system. In our study, some members of transient receptor potential channels have been identified to contribute to substrate rigidity sensing.

Research Products

• [Journal Article] Molecular dynamics study on protein-water interplay in the mechanogating of the bacterial mechanosensitive channel MscL (2015)
  • Author(s): Sawada Y, Sokabe M
  • Journal Title: Eur J Biophys Volume: 44 Issue: 7 Pages: 531-43
  • DOI: 10.1007/s00249-015-1065-2
  • Peer Reviewed / Open Access
• [Journal Article] Unidirectional incorporation of a bacterial mechanosensitive channel into liposomal membranes (2015)
  • Author(s): Nomura T, Cox CD, Bavi N, Sokabe M and Martinac B
  • Journal Title: FASEB J. Volume: 29 Issue: 10 Pages: 4334-45
  • DOI: 10.1096/fj.15-275198
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] FUS regulates AMPA receptor function and FTLD/ALS-associated behaviour via GluA1 mRNA stabilization. (2015)
  • Author(s): Udagawa, T., Fujioka, Y., Tanaka, M., Honda, D., Yokoi, S., Riku, Y., Ibi, D., Nagai, T., Yamada, K., Watanabe, H., Katsuno, M., Inada, T., Ohno, K., Sokabe, M., Okado, H., Ishigaki S*., and Sobue, G.
  • Journal Title: Nat Commun Volume: 6 Issue: 1 Pages: 7098-7098
  • DOI: 10.1038/ncomms8098
  • Peer Reviewed / Open Access
• [Journal Article] Disrupted-in-schizophrenia 1 regulates transport of ITPR1 mRNA for synaptic plasticity. (2015)
  • Author(s): Tsuboi D, Kuroda K, Tanaka M, Namba T, Iizuka Y, Taya S, Shinoda T, Hikita T, Muraoka S, Iizuka M, Nimura A, Mizoguchi A, Shiina N, Sokabe M, Okano H, Mikoshiba K, Kaibuchi K
  • Journal Title: Nature Neuroscience Volume: in press Issue: 5 Pages: 698-707
  • DOI: 10.1038/nn.3984
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Actomyosin bundles serve as a tension sensor and a platform for ERK activation (2015)
  • Author(s): Hirata H, Gupta1 M, Vedula SRK, Lim CT, Ladoux B, Sokabe M
  • Journal Title: EMBO Rep Volume: 16 Issue: 2 Pages: 250-257
  • DOI: 10.15252/embr.201439140
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Proteoglycan from salmon nasal cartridge promotes in vitro wound healing of fibroblast monolayers via the CD44 receptor (2015)
  • Author(s): G. Ito, T. Kobayashi, Y. Takeda, M. Sokabe
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 456 Issue: 3 Pages: 792-798
  • DOI: 10.1016/j.bbrc.2014.12.037
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Congenital myasthenic syndrome in Japan: ethnically unique mutations in muscle nicotinic acetylcholine receptor subunits (2015)
  • Author(s): Azuma Y, Nakata T, Tanaka M, Shen XM, Ito M, Iwata S, Okuno T, Nomura Y, Ando N, Ishigaki K, Ohkawara B, Masuda A, Natsume J, Kojima S, Sokabe M, Ohno K.
  • Journal Title: Neuromuscul Disord Volume: 25(1) Issue: 1 Pages: 60-69
  • DOI: 10.1016/j.nmd.2014.09.002
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Sigma-1 (σ1) receptor deficiency reduces β-amyloid25-35-induced hippocampal neuronal cell death and cognitive deficits through suppressing phosphorylation of the NMDA receptor NR2B (2015)
  • Author(s): Yin J, Sha S, Li L, Wang C, Jie P, Sokabe M, Chen L
  • Journal Title: Neuropharmacol Volume: 89 Pages: 215-224
  • DOI: 10.1016/j.neuropharm.2014.09.027
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Ion channels activated by mechanical forces in bacterial and eukaryotic cells (2015)
  • Author(s): Sokabe M, Sawada M, Kobayashi T
  • Journal Title: Subcell Biochem Volume: 72 Pages: 613-626
  • DOI: 10.1007/978-94-017-9918-8_28
  • ISBN: 9789401799171, 9789401799188
  • Peer Reviewed
• [Journal Article] Non-channel Mechanosensors Working at Focal Adhesion-Stress Fiber Complex (2015)
  • Author(s): Hirata H, Tatsumi H, Hayakawa K, Sokabe M
  • Journal Title: Pflügers Archiv -Eur J Physiol Volume: 467 Issue: 1 Pages: 141-155
  • DOI: 10.1007/s00424-014-1558-3
• [Journal Article] A novel role of actomyosin bundles in ERK signaling (2015)
  • Author(s): Hirata H, Sokabe M
  • Journal Title: Commun Integr Biol Volume: 8 Issue: 2 Pages: e1017176-e1017176
  • DOI: 10.1080/19420889.2015.1017176
• [Journal Article] 発展するメカノセンシング研究 (2015)
  • Author(s): 曽我部正博
  • Journal Title: 血管医学 Volume: 16 Pages: 73-85
• [Journal Article] 骨と筋におけるメカノセンシングとメカノシグナリング (2015)
  • Author(s): 小林剛、曽我部正博
  • Journal Title: The BONE Volume: 29 Pages: 45-53
• [Journal Article] オピニオン：メカノバイオロジーの可能性 (2015)
  • Author(s): 曽我部正博
  • Journal Title: ファルマシア Volume: 51 Pages: 1025-1025
• [Journal Article] アクチン線維は張力を感じ、コフィリンとの相互作用を介して細胞骨格の動態を制御するメカノセンサーである (2015)
  • Author(s): 辰巳仁史、早川公英、曽我部正博
  • Journal Title: 生物物理 Volume: 55 Pages: 187-191
  • NAID: 130005090035
• [Journal Article] New candidates for mechano-sensitive channels potentially (2014)
  • Author(s): H. Iida, T. Furuichi, M. Nakano, M. Toyota, M. Sokabe & H. Tatsumi
  • Journal Title: Plant Biology Volume: 16(Suppl. 1) Issue: s1 Pages: 39-42
  • DOI: 10.1111/plb.12044
  • Peer Reviewed
• [Journal Article] Mechanosensitive channels are activated by stress in the actin stress fibers, which could be involved in gravity sensing in plants (2014)
  • Author(s): Hitoshi Tatsumi, Takuya Furuichi, Masataka Nakano, Masatsugu Toyota, Kimihide Hayakawa, Masahiro Sokabe, and Hidetoshi Iida
  • Journal Title: Plant Biology Volume: 16(Suppl. 1) Issue: s1 Pages: 18-22
  • DOI: 10.1111/plb.12095
  • Peer Reviewed
• [Journal Article] Real-time luminescence imaging of cellular ATP release (2014)
  • Author(s): Furuya K, Sokabe M, Grygorczyk R
  • Journal Title: Real-time luminescence imaging of cellular ATP release Volume: 66 Issue: 2 Pages: 330-344
  • DOI: 10.1016/j.ymeth.2013.08.007
  • Peer Reviewed
• [Journal Article] Force-dependent vinculin binding to talin in live cells: a crucial step in anchoring the actin cytoskeleton to focal adhesions (2014)
  • Author(s): Hiroaki Hirata, Hitoshi Tatsumi, Chwee Teck Lim, and Masahiro Sokabe
  • Journal Title: American Jounal of Physiology Volume: 306 Issue: 6 Pages: 607-20
  • DOI: 10.1152/ajpcell.00122.2013
  • Peer Reviewed / Open Access
• [Journal Article] Analyses of a gravistimulation-specific Ca2+ signature in Arabidopsis using parabolic flights (2013)
  • Author(s): Masatsugu Toyotaa, Takuya Furuichi, Masahiro Sokabea, and Hitoshi Tatsumi
  • Journal Title: Plant Physiology Volume: 163 Issue: 2 Pages: 543-554
  • DOI: 10.1104/pp.113.223313
  • Peer Reviewed / Open Access
• [Journal Article] Bidirectional modulatory effect of 17β-estradiol on NMDA receptors via ERα and ERβ in the dentate gyrus of juvenile male rats (2013)
  • Author(s): Tanaka M, Sokabe M
  • Journal Title: Neuropharmacol Volume: 75 Pages: 262-273
  • DOI: 10.1016/j.neuropharm.2013.07.029
  • Peer Reviewed
• [Journal Article] Imaging and characterization of stretch-induced ATP release from alveolar A549 cells. (2013)
  • Author(s): Grygorczyk R, Furuya K, Sokabe M.
  • Journal Title: J Physiol, Volume: 591 (5) Pages: 1195-1215
  • Peer Reviewed
• [Journal Article] Mechanosensing by actin filaments and focal proteins (2012)
  • Author(s): Hayakawa K, Tatsumi H, Sokabe M
  • Journal Title: Commun Integr Biol Volume: 5(6) Issue: 6 Pages: 572-576
  • DOI: 10.4161/cib.21891
  • Peer Reviewed
• [Journal Article] Martinac B. Differential effects of lipids and lyso-lipids on the mechanosensitivity of MscL and MscS. (2012)
  • Author(s): Nomura T, Cranfield CG, Deplazes E, Owen DM, Macmillan A, Battle AR, Constantine M, Sokabe M
  • Journal Title: Proc Natl Acad Sci, USA, Volume: 109(22) Issue: 7 Pages: 8770-8775
  • DOI: 10.1073/pnas.072632899
  • Peer Reviewed
• [Presentation] Mechanobiology of Wound Healing: Effects of force and extracellular ATP (2015)
  • Author(s): Sokabe M
  • Organizer: The 4th International Conference on Innovative Biology, Medicine, and Engineering (ICIBME Hanoi)
  • Place of Presentation: Hanoi, Vietnam
  • Year and Date: 2015-10-13
  • Int'l Joint Research / Invited
• [Presentation] 細胞から自分を眺める：メカノバイオロジーへの招待 (2015)
  • Author(s): 曽我部正博
  • Organizer: 日本心理学会第79回大会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-09-22
  • Invited
• [Presentation] Mechano-sensing by actin filaments (2015)
  • Author(s): Hayakawa K, Sokabe M , Tatsumi H
  • Organizer: 8th ICCPB
  • Place of Presentation: Kraków, Poland
  • Year and Date: 2015-08-23
  • Int'l Joint Research
• [Presentation] Molecular and biophysical mechanisms underlying force dependent dynamics (breakdown) of actin cytoskeletons (2015)
  • Author(s): Sokabe M
  • Organizer: 7th WACBE World Congress on Bioengineering
  • Place of Presentation: National University of Singapore, Singapore
  • Year and Date: 2015-07-06
• [Presentation] Gating mechanism of bacterial mechanosensitive channels: Interplay between protein, lipid and water (2015)
  • Author(s): Sokabe M, Sawada Y
  • Organizer: The 18th iCeMS International Symposium/ The 15th International Membrane Research Forum : Featuring Meso-Scale Molecular Complexes and Domains and Synaptic Membranes
  • Place of Presentation: iCeMS, Kyoto University, Kyoto, Kyoto
  • Year and Date: 2015-03-02
  • Int'l Joint Research / Invited
• [Presentation] 機械受容チャネルの開閉制御における水の役割 (2015)
  • Author(s): 曽我部正博
  • Organizer: 第2回「水シグナリングの分子動態から病態へ」研究会
  • Place of Presentation: 福井大学文京キャンパス（福井県福井市）
  • Year and Date: 2015-03-02
  • Invited
• [Presentation] Mechano-sensitive ATP release: critical involvement in wound healing (2013)
  • Author(s): Sokabe M
  • Organizer: ICBME2013
  • Place of Presentation: the National University of Singapore University Town, Singapore
  • Year and Date: 2013-12-04 – 2013-12-07
  • Invited
• [Presentation] The versatile roles of actin cytoskeletons in cell mechanosensing (2013)
  • Author(s): Sokabe M
  • Organizer: Special Seminar at the Dept Chemistry, Norwich Univ
  • Place of Presentation: Norwich, UK
  • Year and Date: 2013-07-22
  • Invited
• [Presentation] Cell Mechanosensing: the underlying molecular and biophysical mechanisms and physiological roles (2013)
  • Author(s): Sokabe M
  • Organizer: JASS Seminar
  • Place of Presentation: Riken Singapore Office, Singapore
  • Year and Date: 2013-07-05
  • Invited
• [Presentation] Roles of actin cytoskeleton in cellular mechanotransduction. (2012)
  • Author(s): Sokabe M
  • Organizer: Symposium on “Force Transduction and Emerging Channels
  • Place of Presentation: Berlin/Germany
  • Invited
• [Book] Recent Advances in Mechanobiology (2012)
  • Author(s): Sokabe M, Sawada Y, Nomura K, Yoshimura K, Kobayashi T.
  • Total Pages: 200
  • Publisher: Shanghai Sci Tech Liter Pub House