@article{b40860f8dc2745ca9de082fcd09a8261,
title = "Caldesmon controls stress fiber force-balance through dynamic cross-linking of myosin II and actin-tropomyosin filaments",
abstract = "Contractile actomyosin bundles are key force-producing and mechanosensing elements in muscle and non-muscle tissues. Whereas the organization of muscle myofibrils and mechanism regulating their contractility are relatively well-established, the principles by which myosin-II activity and force-balance are regulated in non-muscle cells have remained elusive. We show that Caldesmon, an important component of smooth muscle and non-muscle cell actomyosin bundles, is an elongated protein that functions as a dynamic cross-linker between myosin-II and tropomyosin-actin filaments. Depletion of Caldesmon results in aberrant lateral movement of myosin-II filaments along actin bundles, leading to irregular myosin distribution within stress fibers. This manifests as defects in stress fiber network organization and contractility, and accompanied problems in cell morphogenesis, migration, invasion, and mechanosensing. These results identify Caldesmon as critical factor that ensures regular myosin-II spacing within non-muscle cell actomyosin bundles, and reveal how stress fiber networks are controlled through dynamic cross-linking of tropomyosin-actin and myosin filaments.",
author = "Kokate, {Shrikant B.} and Katarzyna Ciuba and Tran, {Vivien D.} and Reena Kumari and Sari Tojkander and Ulrike Engel and Konstantin Kogan and Sanjay Kumar and Pekka Lappalainen",
note = "Funding Information: This work is supported by grants from the Sigrid Jus{\'e}lius Foundation (4708344) and Academy of Finland (302161 and 346133) (to P.L.), NIH R01GM122375 grant (to S.K.), and NSF Graduate Research Fellowship Program (to V.D.T.). We thank the technical staff at the Institute of Biotechnology Light Microscopy Unit (LMU) and Biomedicum Imaging Unit (BIU) for the technical support in microscopy and image analysis. We also thank Mirva Tirkkonen for technical assistance. Confocal and 2-photon imaging experiments for the laser nanosurgery were conducted at the CRL Molecular Imaging Center at UC Berkeley, RRID:SCR_017852, supported by NSF DBI-1041078. We thank Holly Aaron and Feather Ives for their microscopy advice and support. Funding Information: This work is supported by grants from the Sigrid Jus{\'e}lius Foundation (4708344) and Academy of Finland (302161 and 346133) (to P.L.), NIH R01GM122375 grant (to S.K.), and NSF Graduate Research Fellowship Program (to V.D.T.). We thank the technical staff at the Institute of Biotechnology Light Microscopy Unit (LMU) and Biomedicum Imaging Unit (BIU) for the technical support in microscopy and image analysis. We also thank Mirva Tirkkonen for technical assistance. Confocal and 2-photon imaging experiments for the laser nanosurgery were conducted at the CRL Molecular Imaging Center at UC Berkeley, RRID:SCR_017852, supported by NSF DBI-1041078. We thank Holly Aaron and Feather Ives for their microscopy advice and support. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = oct,
doi = "10.1038/s41467-022-33688-w",
language = "English",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Research",
}