The titin N2B and N2A regions: biomechanical and metabolic signaling hubs in cross-striated muscles (2024)

van der Pijl, R. J., Domenighetti, A. A., Sheikh, F., Ehler, E., Ottenheijm, C. A. C. (2021). The titin N2B and N2A regions: biomechanical and metabolic signaling hubs in cross-striated muscles. Biophysical Reviews, 13(5), 653-677. https://doi.org/10.1007/s12551-021-00836-3

van der Pijl, Robbert J ; Domenighetti, Andrea A ; Sheikh, Farah et al. / The titin N2B and N2A regions : biomechanical and metabolic signaling hubs in cross-striated muscles. In: Biophysical Reviews. 2021 ; Vol. 13, No. 5. pp. 653-677.

@article{bb3c05208a464b10bc42b91e4d8edd45,

title = "The titin N2B and N2A regions: biomechanical and metabolic signaling hubs in cross-striated muscles",

abstract = "Muscle specific signaling has been shown to originate from myofilaments and their associated cellular structures, including the sarcomeres, costameres or the cardiac intercalated disc. Two signaling hubs that play important biomechanical roles for cardiac and/or skeletal muscle physiology are the N2B and N2A regions in the giant protein titin. Prominent proteins associated with these regions in titin are chaperones Hsp90 and αB-crystallin, members of the four-and-a-half LIM (FHL) and muscle ankyrin repeat protein (Ankrd) families, as well as thin filament-associated proteins, such as myopalladin. This review highlights biological roles and properties of the titin N2B and N2A regions in health and disease. Special emphasis is placed on functions of Ankrd and FHL proteins as mechanosensors that modulate muscle-specific signaling and muscle growth. This region of the sarcomere also emerged as a hotspot for the modulation of passive muscle mechanics through altered titin phosphorylation and splicing, as well as tethering mechanisms that link titin to the thin filament system.",

keywords = "Mechanosensor, Muscle, Muscle mechanics, Sarcomere, Signaling, Titin",

author = "{van der Pijl}, {Robbert J} and Domenighetti, {Andrea A} and Farah Sheikh and Elisabeth Ehler and Ottenheijm, {Coen A C} and Stephan Lange",

note = "{\textcopyright} The Author(s) 2021.",

year = "2021",

month = oct,

doi = "10.1007/s12551-021-00836-3",

language = "English",

volume = "13",

pages = "653--677",

journal = "Biophysical Reviews",

issn = "1867-2450",

publisher = "Springer",

number = "5",

}

van der Pijl, RJ, Domenighetti, AA, Sheikh, F, Ehler, E, Ottenheijm, CAC 2021, 'The titin N2B and N2A regions: biomechanical and metabolic signaling hubs in cross-striated muscles', Biophysical Reviews, vol. 13, no. 5, pp. 653-677. https://doi.org/10.1007/s12551-021-00836-3

The titin N2B and N2A regions: biomechanical and metabolic signaling hubs in cross-striated muscles. / van der Pijl, Robbert J; Domenighetti, Andrea A; Sheikh, Farah et al.
In: Biophysical Reviews, Vol. 13, No. 5, 10.2021, p. 653-677.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Review › Research › peer-review

TY - JOUR

T1 - The titin N2B and N2A regions

T2 - biomechanical and metabolic signaling hubs in cross-striated muscles

AU - van der Pijl, Robbert J

AU - Domenighetti, Andrea A

AU - Sheikh, Farah

AU - Ehler, Elisabeth

AU - Ottenheijm, Coen A C

AU - Lange, Stephan

N1 - © The Author(s) 2021.

PY - 2021/10

Y1 - 2021/10

N2 - Muscle specific signaling has been shown to originate from myofilaments and their associated cellular structures, including the sarcomeres, costameres or the cardiac intercalated disc. Two signaling hubs that play important biomechanical roles for cardiac and/or skeletal muscle physiology are the N2B and N2A regions in the giant protein titin. Prominent proteins associated with these regions in titin are chaperones Hsp90 and αB-crystallin, members of the four-and-a-half LIM (FHL) and muscle ankyrin repeat protein (Ankrd) families, as well as thin filament-associated proteins, such as myopalladin. This review highlights biological roles and properties of the titin N2B and N2A regions in health and disease. Special emphasis is placed on functions of Ankrd and FHL proteins as mechanosensors that modulate muscle-specific signaling and muscle growth. This region of the sarcomere also emerged as a hotspot for the modulation of passive muscle mechanics through altered titin phosphorylation and splicing, as well as tethering mechanisms that link titin to the thin filament system.

AB - Muscle specific signaling has been shown to originate from myofilaments and their associated cellular structures, including the sarcomeres, costameres or the cardiac intercalated disc. Two signaling hubs that play important biomechanical roles for cardiac and/or skeletal muscle physiology are the N2B and N2A regions in the giant protein titin. Prominent proteins associated with these regions in titin are chaperones Hsp90 and αB-crystallin, members of the four-and-a-half LIM (FHL) and muscle ankyrin repeat protein (Ankrd) families, as well as thin filament-associated proteins, such as myopalladin. This review highlights biological roles and properties of the titin N2B and N2A regions in health and disease. Special emphasis is placed on functions of Ankrd and FHL proteins as mechanosensors that modulate muscle-specific signaling and muscle growth. This region of the sarcomere also emerged as a hotspot for the modulation of passive muscle mechanics through altered titin phosphorylation and splicing, as well as tethering mechanisms that link titin to the thin filament system.

KW - Mechanosensor

KW - Muscle

KW - Muscle mechanics

KW - Sarcomere

KW - Signaling

KW - Titin

U2 - 10.1007/s12551-021-00836-3

DO - 10.1007/s12551-021-00836-3

M3 - Review

C2 - 34745373

SN - 1867-2450

VL - 13

SP - 653

EP - 677

JO - Biophysical Reviews

JF - Biophysical Reviews

IS - 5

ER -

van der Pijl RJ, Domenighetti AA, Sheikh F, Ehler E, Ottenheijm CAC, Lange S. The titin N2B and N2A regions: biomechanical and metabolic signaling hubs in cross-striated muscles. Biophysical Reviews. 2021 Oct;13(5):653-677. doi: 10.1007/s12551-021-00836-3