Assembly of Peripheral Actomyosin Bundles in Epithelial Cells Is Dependent on the CaMKK2/AMPK Pathway

• Published in: Cell reports (Cambridge) Vol. 30; no. 12; pp. 4266 - 4280.e4
• Main Authors: Rajakylä, Eeva Kaisa, Lehtimäki, Jaakko I., Acheva, Anna, Schaible, Niccole, Lappalainen, Pekka, Krishnan, Ramaswamy, Tojkander, Sari
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.03.2020; Elsevier
• Subjects: actin; Actins - metabolism; Actomyosin - metabolism; actomyosin bundles; adhesive structures; AMP-Activated Protein Kinases - metabolism; AMPK; Animals; Biomechanical Phenomena; Cadherins - metabolism; Calcium-Calmodulin-Dependent Protein Kinase Kinase - metabolism; CaMKK2; Cell Adhesion Molecules; Cell Communication; Cell Line; Cell Movement; Cell Polarity; Cells, Cultured; cellular forces; Dogs; Enzyme Activation; epithelia; Epithelial Cells - cytology; Epithelial Cells - metabolism; epithelial integrity; Epithelial-Mesenchymal Transition; Female; Humans; mechanosensing; Microfilament Proteins; Models, Biological; myosin; Phenotype; Phosphoproteins; Signal Transduction; stress fibers; Stress Fibers - metabolism; Up-Regulation; cellular forces; mechanosensing; actin; epithelial integrity; actomyosin bundles; adhesive structures; myosin; AMPK; CaMKK2; epithelia; stress fibers
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.02.096

Defects in the maintenance of intercellular junctions are associated with loss of epithelial barrier function and consequent pathological conditions, including invasive cancers. Epithelial integrity is dependent on actomyosin bundles at adherens junctions, but the origin of these junctional bundles is incompletely understood. Here we show that peripheral actomyosin bundles can be generated from a specific actin stress fiber subtype, transverse arcs, through their lateral fusion at cell-cell contacts. Importantly, we find that assembly and maintenance of peripheral actomyosin bundles are dependent on the mechanosensitive CaMKK2/AMPK signaling pathway and that inhibition of this route leads to disruption of tension-maintaining actomyosin bundles and re-growth of stress fiber precursors. This results in redistribution of cellular forces, defects in monolayer integrity, and loss of epithelial identity. These data provide evidence that the mechanosensitive CaMKK2/AMPK pathway is critical for the maintenance of peripheral actomyosin bundles and thus dictates cell-cell junctions through cellular force distribution. [Display omitted] •Peripheral actomyosin bundles can be formed from a specific stress fiber subtype•Maintenance of these bundles is dependent on mechanosensitive CaMKK2/AMPK pathway•Inhibition of CaMKK2/AMPK pathway leads to redistribution of cellular forces Rajakylä et al. show that in epithelial cell cultures, peripheral actomyosin bundles are generated from a specific actin stress fiber type, transverse arcs. Bundle assembly is triggered by a mechanosensitive Ca2+/CaMKK2/AMPK pathway upon cell confluency. Inhibition of this route causes altered cellular force distribution and loss of epithelial cell identity.