Caldwell Benjamin J, Lucas Christine, Kee Anthony J, Gaus Katharina, Gunning Peter W, Hardeman Edna C, Yap Alpha S, Gomez Guillermo A
Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
Cytoskeleton (Hoboken). 2014 Dec;71(12):663-76. doi: 10.1002/cm.21202. Epub 2015 Jan 31.
Epithelial cells generate contractile forces at their cell-cell contacts. These are concentrated at the specialized apical junction of the zonula adherens (ZA), where a ring of stabilized E-cadherin lies adjacent to prominent actomyosin bundles. Coupling of adhesion and actomyosin contractility yields tension in the junction. The biogenesis of junctional contractility requires actin assembly at the ZA as well as the recruitment of nonmuscle myosin II, but the molecular regulators of these processes are not yet fully understood. We now report a role for tropomyosins 5NM1 (Tm5NM1) and 5NM2 (Tm5NM2) in their generation. Both these tropomyosin isoforms were found at the ZA and their depletion by RNAi or pharmacological inhibition reduced both F-actin and myosin II content at the junction. Photoactivation analysis revealed that the loss of F-actin was attributable to a decrease in filament stability. These changes were accompanied by a decrease in E-cadherin content at junctions. Ultimately, both long-term depletion of Tm5NM1/2 and acute inhibition with drugs caused junctional tension to be reduced. Thus these tropomyosin isoforms are novel contributors to junctional contractility and integrity.
上皮细胞在其细胞间接触部位产生收缩力。这些收缩力集中在黏着小带（ZA）的特化顶端连接处，在那里，一圈稳定的E-钙黏蛋白紧邻突出的肌动球蛋白束。黏附与肌动球蛋白收缩性的耦合在连接处产生张力。连接处收缩性的生物发生需要在ZA处进行肌动蛋白组装以及募集非肌肉肌球蛋白II，但这些过程的分子调节因子尚未完全了解。我们现在报道原肌球蛋白5NM1（Tm5NM1）和5NM2（Tm5NM2）在其产生过程中的作用。在ZA处发现了这两种原肌球蛋白异构体，通过RNA干扰或药物抑制使其耗竭会降低连接处的F-肌动蛋白和肌球蛋白II含量。光活化分析表明，F-肌动蛋白的减少归因于细丝稳定性的降低。这些变化伴随着连接处E-钙黏蛋白含量的减少。最终，长期耗尽Tm5NM1/2以及用药物进行急性抑制都会导致连接处张力降低。因此，这些原肌球蛋白异构体是连接处收缩性和完整性的新贡献者。
