ZAKβ is activated by cellular compression and mediates contraction-induced MAP kinase signaling in skeletal muscle

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

ZAKβ is activated by cellular compression and mediates contraction-induced MAP kinase signaling in skeletal muscle. / Nordgaard, Cathrine; Vind, Anna Constance; Stonadge, Amy; Kjøbsted, Rasmus; Snieckute, Goda; Antas, Pedro; Blasius, Melanie; Reinert, Marie Sofie; Del Val, Ana Martinez; Bekker-Jensen, Dorte Breinholdt; Haahr, Peter; Miroshnikova, Yekaterina A; Mazouzi, Abdelghani; Falk, Sarah; Perrier-Groult, Emeline; Tiedje, Christopher; Li, Xiang; Jakobsen, Jens Rithamer; Jørgensen, Nicolas Oldenburg; Wojtaszewski, Jørgen; Mallein-Gerin, Frederic; Andersen, Jesper Løvind; Pennisi, Cristian Pablo; Clemmensen, Christoffer; Kassem, Moustapha; Jafari, Abbas; Brummelkamp, Thijn; Li, Vivian Sw; Wickström, Sara A; Olsen, Jesper Velgaard; Blanco, Gonzalo; Bekker-Jensen, Simon.

In: E M B O Journal, Vol. 41, No. 17, e111650, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Nordgaard, C, Vind, AC, Stonadge, A, Kjøbsted, R, Snieckute, G, Antas, P, Blasius, M, Reinert, MS, Del Val, AM, Bekker-Jensen, DB, Haahr, P, Miroshnikova, YA, Mazouzi, A, Falk, S, Perrier-Groult, E, Tiedje, C, Li, X, Jakobsen, JR, Jørgensen, NO, Wojtaszewski, J, Mallein-Gerin, F, Andersen, JL, Pennisi, CP, Clemmensen, C, Kassem, M, Jafari, A, Brummelkamp, T, Li, VS, Wickström, SA, Olsen, JV, Blanco, G & Bekker-Jensen, S 2022, 'ZAKβ is activated by cellular compression and mediates contraction-induced MAP kinase signaling in skeletal muscle', E M B O Journal, vol. 41, no. 17, e111650. https://doi.org/10.15252/embj.2022111650

APA

Nordgaard, C., Vind, A. C., Stonadge, A., Kjøbsted, R., Snieckute, G., Antas, P., Blasius, M., Reinert, M. S., Del Val, A. M., Bekker-Jensen, D. B., Haahr, P., Miroshnikova, Y. A., Mazouzi, A., Falk, S., Perrier-Groult, E., Tiedje, C., Li, X., Jakobsen, J. R., Jørgensen, N. O., ... Bekker-Jensen, S. (2022). ZAKβ is activated by cellular compression and mediates contraction-induced MAP kinase signaling in skeletal muscle. E M B O Journal, 41(17), [e111650]. https://doi.org/10.15252/embj.2022111650

Vancouver

Nordgaard C, Vind AC, Stonadge A, Kjøbsted R, Snieckute G, Antas P et al. ZAKβ is activated by cellular compression and mediates contraction-induced MAP kinase signaling in skeletal muscle. E M B O Journal. 2022;41(17). e111650. https://doi.org/10.15252/embj.2022111650

Author

Nordgaard, Cathrine ; Vind, Anna Constance ; Stonadge, Amy ; Kjøbsted, Rasmus ; Snieckute, Goda ; Antas, Pedro ; Blasius, Melanie ; Reinert, Marie Sofie ; Del Val, Ana Martinez ; Bekker-Jensen, Dorte Breinholdt ; Haahr, Peter ; Miroshnikova, Yekaterina A ; Mazouzi, Abdelghani ; Falk, Sarah ; Perrier-Groult, Emeline ; Tiedje, Christopher ; Li, Xiang ; Jakobsen, Jens Rithamer ; Jørgensen, Nicolas Oldenburg ; Wojtaszewski, Jørgen ; Mallein-Gerin, Frederic ; Andersen, Jesper Løvind ; Pennisi, Cristian Pablo ; Clemmensen, Christoffer ; Kassem, Moustapha ; Jafari, Abbas ; Brummelkamp, Thijn ; Li, Vivian Sw ; Wickström, Sara A ; Olsen, Jesper Velgaard ; Blanco, Gonzalo ; Bekker-Jensen, Simon. / ZAKβ is activated by cellular compression and mediates contraction-induced MAP kinase signaling in skeletal muscle. In: E M B O Journal. 2022 ; Vol. 41, No. 17.

Bibtex

@article{a33081335d5045999c6a79c4e18ea125,

title = "ZAKβ is activated by cellular compression and mediates contraction-induced MAP kinase signaling in skeletal muscle",

abstract = "Mechanical inputs give rise to p38 and JNK activation, which mediate adaptive physiological responses in various tissues. In skeletal muscle, contraction-induced p38 and JNK signaling ensure adaptation to exercise, muscle repair, and hypertrophy. However, the mechanisms by which muscle fibers sense mechanical load to activate this signaling have remained elusive. Here, we show that the upstream MAP3K ZAKβ is activated by cellular compression induced by osmotic shock and cyclic compression in vitro, and muscle contraction in vivo. This function relies on ZAKβ's ability to recognize stress fibers in cells and Z-discs in muscle fibers when mechanically perturbed. Consequently, ZAK-deficient mice present with skeletal muscle defects characterized by fibers with centralized nuclei and progressive adaptation towards a slower myosin profile. Our results highlight how cells in general respond to mechanical compressive load and how mechanical forces generated during muscle contraction are translated into MAP kinase signaling.",

keywords = "Faculty of Science, Mechanobiology, Muscle contraction, Myopathy, ZAKβ",

author = "Cathrine Nordgaard and Vind, {Anna Constance} and Amy Stonadge and Rasmus Kj{\o}bsted and Goda Snieckute and Pedro Antas and Melanie Blasius and Reinert, {Marie Sofie} and {Del Val}, {Ana Martinez} and Bekker-Jensen, {Dorte Breinholdt} and Peter Haahr and Miroshnikova, {Yekaterina A} and Abdelghani Mazouzi and Sarah Falk and Emeline Perrier-Groult and Christopher Tiedje and Xiang Li and Jakobsen, {Jens Rithamer} and J{\o}rgensen, {Nicolas Oldenburg} and J{\o}rgen Wojtaszewski and Frederic Mallein-Gerin and Andersen, {Jesper L{\o}vind} and Pennisi, {Cristian Pablo} and Christoffer Clemmensen and Moustapha Kassem and Abbas Jafari and Thijn Brummelkamp and Li, {Vivian Sw} and Wickstr{\"o}m, {Sara A} and Olsen, {Jesper Velgaard} and Gonzalo Blanco and Simon Bekker-Jensen",

note = "{\textcopyright} 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.",

year = "2022",

doi = "10.15252/embj.2022111650",

language = "English",

volume = "41",

journal = "E M B O Journal",

issn = "0261-4189",

publisher = "Wiley-Blackwell",

number = "17",

}

RIS

TY - JOUR

T1 - ZAKβ is activated by cellular compression and mediates contraction-induced MAP kinase signaling in skeletal muscle

AU - Nordgaard, Cathrine

AU - Vind, Anna Constance

AU - Stonadge, Amy

AU - Kjøbsted, Rasmus

AU - Snieckute, Goda

AU - Antas, Pedro

AU - Blasius, Melanie

AU - Reinert, Marie Sofie

AU - Del Val, Ana Martinez

AU - Bekker-Jensen, Dorte Breinholdt

AU - Haahr, Peter

AU - Miroshnikova, Yekaterina A

AU - Mazouzi, Abdelghani

AU - Falk, Sarah

AU - Perrier-Groult, Emeline

AU - Tiedje, Christopher

AU - Li, Xiang

AU - Jakobsen, Jens Rithamer

AU - Jørgensen, Nicolas Oldenburg

AU - Wojtaszewski, Jørgen

AU - Mallein-Gerin, Frederic

AU - Andersen, Jesper Løvind

AU - Pennisi, Cristian Pablo

AU - Clemmensen, Christoffer

AU - Kassem, Moustapha

AU - Jafari, Abbas

AU - Brummelkamp, Thijn

AU - Li, Vivian Sw

AU - Wickström, Sara A

AU - Olsen, Jesper Velgaard

AU - Blanco, Gonzalo

AU - Bekker-Jensen, Simon

PY - 2022

Y1 - 2022

N2 - Mechanical inputs give rise to p38 and JNK activation, which mediate adaptive physiological responses in various tissues. In skeletal muscle, contraction-induced p38 and JNK signaling ensure adaptation to exercise, muscle repair, and hypertrophy. However, the mechanisms by which muscle fibers sense mechanical load to activate this signaling have remained elusive. Here, we show that the upstream MAP3K ZAKβ is activated by cellular compression induced by osmotic shock and cyclic compression in vitro, and muscle contraction in vivo. This function relies on ZAKβ's ability to recognize stress fibers in cells and Z-discs in muscle fibers when mechanically perturbed. Consequently, ZAK-deficient mice present with skeletal muscle defects characterized by fibers with centralized nuclei and progressive adaptation towards a slower myosin profile. Our results highlight how cells in general respond to mechanical compressive load and how mechanical forces generated during muscle contraction are translated into MAP kinase signaling.

AB - Mechanical inputs give rise to p38 and JNK activation, which mediate adaptive physiological responses in various tissues. In skeletal muscle, contraction-induced p38 and JNK signaling ensure adaptation to exercise, muscle repair, and hypertrophy. However, the mechanisms by which muscle fibers sense mechanical load to activate this signaling have remained elusive. Here, we show that the upstream MAP3K ZAKβ is activated by cellular compression induced by osmotic shock and cyclic compression in vitro, and muscle contraction in vivo. This function relies on ZAKβ's ability to recognize stress fibers in cells and Z-discs in muscle fibers when mechanically perturbed. Consequently, ZAK-deficient mice present with skeletal muscle defects characterized by fibers with centralized nuclei and progressive adaptation towards a slower myosin profile. Our results highlight how cells in general respond to mechanical compressive load and how mechanical forces generated during muscle contraction are translated into MAP kinase signaling.

KW - Faculty of Science

KW - Mechanobiology

KW - Muscle contraction

KW - Myopathy

KW - ZAKβ

U2 - 10.15252/embj.2022111650

DO - 10.15252/embj.2022111650

M3 - Journal article

C2 - 35899396

VL - 41

JO - E M B O Journal

JF - E M B O Journal

SN - 0261-4189

IS - 17

M1 - e111650

ER -

ID: 315182860