형광공명에너지전이 알파카테닌 센서를 활용한 세포 부착접합부에서의 힘 전달 이미징

장윤관; 서정수; 석명은; 김태진; Yoon-Kwan Jang; Jung-Soo Suh; Myungeun Suk; Tae-Jin Kim

Korean Chemical Engineering Research, Vol.59, No.3, 366-372, August, 2021

DOI10.9713/kcer.2021.59.3.366 Export Citation

형광공명에너지전이 알파카테닌 센서를 활용한 세포 부착접합부에서의 힘 전달 이미징

Force Transmission in Cellular Adherens Junction Visualized by Engineered FRET Alpha-catenin Sensor

장윤관^{1, 2}, 서정수^{1, 2}, 석명은^{3, †}, 김태진^{1, 2, †}

¹부산대학교 자연과학대학 생명시스템학과, 46241 부산광역시 금정구 부산대학로 63번길 2
²부산대학교 자연과학대학 생명과학과, 46241 부산광역시 금정구 부산대학로 63번길 2
³동의대학교 IT융합부품소재공과대학 기계공학과, 47340 부산광역시 부산진구 엄광로 176

Yoon-Kwan Jang^{1, 2}, Jung-Soo Suh^{1, 2}, Myungeun Suk^{3, †}, and Tae-Jin Kim^{1, 2, †}

¹Department of Integrated Biological Science, Pusan National University, 2 Busandaehak-ro 63beon-gil, Geumjeong-gu, Busan, 46241, Korea
²Department of Biological Sciences, Pusan National University, 2 Busandaehak-ro 63beon-gil, Geumjeong-gu, Busan, 46241, Korea
³Department of Mechanical Engineering, IT Convergence College of Components and Materials Engineering, Dong-Eui University, 176, Eomgwang-ro, Busanjingu, Busan, 47340, Korea

E-mail:,

초록

캐드헤린-카테닌 복합체는 세포의 부착 접합부에서 힘의 전달에 중요한 역할을 하는 것으로 생각된다. 그러나 기계적 힘 신호를 시각화 하고 감지하는 적절한 도구의 부재로, 캐드헤린-카테닌 복합체가 세포 간 접합에서 힘 전달을 조절하는 기본 메커니즘은 아직 파악하기가 어렵다. 본 연구에서는 형광공명에너지전이를 기반으로 설계된 알파카테닌센서를 사용하여 캐드헤린에 의해 매개되는 힘 전달을 시각화 하였다. 이러한 결과는 알파카테닌이 세포-세포 접합부에서 캐드헤린 매개 기계적에너지변환(mechanotransduction) 경로의 핵심적인 힘 트랜스듀서(force transducer) 임을 보여준다. 본 연구는 향후 기계적 힘의 세포-세포 상호간의 의사소통에 미치는 영향과 생리학적/병리학적 현상과의 관계를 연구하는 데 중요한 이해를 제공할 것이라 본다.

Cadherin-Catenin complex is thought to play an essential role in the transmission of force at adherens junction. Due to the lack of proper tools to visualize and detect mechanical force signals, the underlying mechanism by which the cadherin-catenin complex regulates force transmission at intercellular junctions remains elusive. In this study, we visualize cadherin-mediated force transmission using an engineered α-Catenin sensor based on fluorescence resonance energy transfer. Our results reveal that α-catenin is a key force transducer in cadherin-mediated mechanotransduction at cell-cell junctions. Thus, our finding will provide important insights for studying the effects of chemical and physical signals on cell-cell communication and the relationship between physiological and pathological phenomena.

Keywords:α-catenin;Fluorescence resonance energy transfer (FRET);Live cell imaging;Traction force;Shear stress

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[2] Mittelbrunn M, Sanchez-Madrid F, Nat. Rev. Mol. Cell Biol., 13(5), 328 (2012)

[3] Meng W, Takeichi M, Cold Spring Harbor Perspect. Biol., 1(6), a00289 (2009)

[4] Vining KH, Mooney DJ, Nat. Rev. Mol. Cell Biol., 18(12), 728 (2017)

[5] Leckband DE, De Rooij J, Annu. Rev. Cell Dev. Biol., 30, 291 (2014)

[6] Ladoux B, Nelson WJ, Yan J, Mege RM, Integr. Biol., 7(10), 1109 (2015)

[7] Yonemura S, Wada Y, Watanabe T, Nagafuchi A, Shibata M, Nat. Cell Biol., 12(6), 533 (2010)

[8] Mei L, de Los Reyes SE, Reynolds MJ, Leicher R, Liu S, Alushin GM, Elife, 9, e62514 (2020)

[9] Leckband DE, In Molecular and Cellular Mechanobiology, New York, 57 (2016).

[10] McCrea PD, Maher MT, Gottardi CJ, Curr. Top. Dev. Biol., 112, 129 (2015)

[11] Ishiyama N, Sarpal R, Wood MN, Barrick SK, et al., Nat. Commun., 9(1), 1 (2018)

[12] Kobielak A, Fuchs E, Nat. Rev. Mol. Cell Biol., 5, 614 (2004)

[13] Kim TJ, Zheng S, Sun J, Muhamed I, Wu J, Lei L, Kong X, Leckband DE, Wang Y, Curr. Biol., 25(2), 218 (2015)

[14] Kim TJ, Seong J, Ouyang M, Sun J, Lu S, Hong JP, Wang N, Wang Y, J. Cell Physiol., 218(2), 285 (2009)

[15] Kim TJ, Sun J, Lu S, Qi YX, Wang Y, PLoS One, 9(10), e10937 (2014)

[16] Kim TJ, Sun J, Lu S, Zhang J, Wang Y, Biomaterials, 35(29), 8348 (2014)

[17] Kim TJ, Lei L, Seong J, Suh JS, Jang YK, Jung SH, Sun J, Kim DH, Wang Y, Adv. Sci., 6(4), 180129 (2019)

[18] Schwarz US, Soine JR, Bioch. Biophys. Acta., 1853(11), 3095 (2015)

[19] Poh YC, Shevtsov SP, Chowdhury F, Wu DC, Na S, Dundr M, Wang N, Nat. Commun., 3(1), 1 (2012)

[20] Liu B, Lu S, Hu YL, Liao X, Ouyang M, Wang Y, Sci. Rep., 4(1), 1 (2014)

[21] Wang Y, Chang J, Li YC, Li YS, Shyy JYJ, Chien S, Am. J. Physiol. Heart Circ. Physiol., 286(2), H685 (2004)

[22] Liu B, Kim TJ, Wang Y, J. R. Soc. Interface., 7(suppl_3), S365 (2010).

[23] Thomas WA, Boscher C, Chu YS, Cuvelier D, Martinez-Rico C, et al., J. Biol. Chem., 288(7), 4957 (2013)

[24] Vermeulen SJ, Bruyneel EA, Bracke ME, De Bruyne G, et al., Cancer Res., 55, 4722 (1995)

[25] Style RW, Boltyanskiy R, German GK, Hyland C, Mac-Minn CW, Mertz AF, Wilen LA, Xu Y, Soft Matter, 10(23), 4047 (2014)