title: Actomyosin contractility provokes contact inhibition in E-cadherin-ligated keratinocytes.
abstract: Confluence-dependent inhibition of epithelial cell proliferation, termed contact inhibition, is crucial for epithelial homeostasis and organ size control. Here we report that among epithelial cells, keratinocytes, which compose the stratified epithelium in the skin, possess a unique, actomyosin-dependent mechanism for contact inhibition. We have observed that under actomyosin-inhibited conditions, cell-cell contact itself through E-cadherin promotes proliferation of keratinocytes. Actomyosin activity in confluent keratinocytes, however, inhibits nuclear localization of β-catenin and YAP, and causes attenuation of β-catenin- and YAP-driven cell proliferation. Confluent keratinocytes develop E-cadherin-mediated punctate adhesion complexes, to which radial actin cables are connected. Eliminating the actin-to-E-cadherin linkage by depleting α-catenin increases proliferation of confluent keratinocytes. By contrast, enforced activation of RhoA-regulated actomyosin or external application of pulling force to ligated E-cadherin attenuates their proliferation, suggesting that tensile stress at E-cadherin-mediated adhesion complexes inhibits proliferation of confluent keratinocytes. Our results highlight actomyosin contractility as a crucial factor that provokes confluence-dependent inhibition of keratinocyte proliferation.
authors.affiliation: R-Pharm Japan, Tokyo 105-0001, Japan.|Mechanobiology Laboratory, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hirata
authors.affiliation: R-Pharm, Moscow 123317, Russia.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Samsonov
authors.affiliation: Mechanobiology Laboratory, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sokabe
mesh_terms: D000205:Actomyosin / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D057809:HEK293 Cells; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D051178:alpha Catenin / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; C456659:YY1AP1 protein, human; D051178:alpha Catenin; D051176:beta Catenin; D000205:Actomyosin