Nonmuscle myosin IIA dynamically guides regulatory light chain phosphorylation and assembly of nonmuscle myosin IIB

• Verfasst von: Weißenbruch, Kai [VerfasserIn]
• Verfasst von: Fladung, Magdalena [VerfasserIn]
• Verfasst von: Grewe, Justin [VerfasserIn]
• Verfasst von: Baulesch, Laurent [VerfasserIn]
• Verfasst von: Schwarz, Ulrich S. [VerfasserIn]
• Verfasst von: Bastmeyer, Martin [VerfasserIn]
• Titel: Nonmuscle myosin IIA dynamically guides regulatory light chain phosphorylation and assembly of nonmuscle myosin IIB
• Verf.angabe: Kai Weißenbruch, Magdalena Fladung, Justin Grewe, Laurent Baulesch, Ulrich S. Schwarz, Martin Bastmeyer
• E-Jahr: 2022
• Jahr: 2 March 2022
• Umfang: 15 S.
• Fussnoten: Gesehen am 26.10.2022
• Titel Quelle: Enthalten in: European journal of cell biology
• Ort Quelle: München : Elsevier, 1998
• Jahr Quelle: 2022
• Band/Heft Quelle: 101(2022), 2, Artikel-ID 151213, Seite 1-15
• ISSN Quelle: 1618-1298
• DOI: doi:10.1016/j.ejcb.2022.151213
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Actomyosin
• Sach-SW: Cellular force generation
• Sach-SW: Mechanobiology
• Sach-SW: Minifilaments
• Sach-SW: Nonmuscle myosin II
• Sach-SW: Paralogs
• K10plus-PPN: 180409370X

Abstract

Nonmuscle myosin II minifilaments have emerged as central elements for force generation and mechanosensing by mammalian cells. Each minifilament can have a different composition and activity due to the existence of the three nonmuscle myosin II paralogs A, B and C and their respective phosphorylation pattern. We have used CRISPR/Cas9-based knockout cells, quantitative image analysis and mathematical modeling to dissect the dynamic processes that control the formation and activity of heterotypic minifilaments and found a strong asymmetry between paralogs A and B. Loss of NM IIA completely abrogates regulatory light chain phosphorylation and reduces the level of assembled NM IIB. Activated NM IIB preferentially co-localizes with pre-formed NM IIA minifilaments and stabilizes the filament in a force-dependent mechanism. NM IIC is only weakly coupled to these processes. We conclude that NM IIA and B play clearly defined complementary roles during assembly of functional minifilaments. NM IIA is responsible for the formation of nascent pioneer minifilaments. NM IIB incorporates into these and acts as a clutch that limits the force output to prevent excessive NM IIA activity. Together these two paralogs form a balanced system for regulated force generation.