title: Junctional actin assembly is mediated by Formin-like 2 downstream of Rac1.
abstract: Epithelial integrity is vitally important, and its deregulation causes early stage cancer. De novo formation of an adherens junction (AJ) between single epithelial cells requires coordinated, spatial actin dynamics, but the mechanisms steering nascent actin polymerization for cell-cell adhesion initiation are not well understood. Here we investigated real-time actin assembly during daughter cell-cell adhesion formation in human breast epithelial cells in 3D environments. We identify formin-like 2 (FMNL2) as being specifically required for actin assembly and turnover at newly formed cell-cell contacts as well as for human epithelial lumen formation. FMNL2 associates with components of the AJ complex involving Rac1 activity and the FMNL2 C terminus. Optogenetic control of Rac1 in living cells rapidly drove FMNL2 to epithelial cell-cell contact zones. Furthermore, Rac1-induced actin assembly and subsequent AJ formation critically depends on FMNL2. These data uncover FMNL2 as a driver for human epithelial AJ formation downstream of Rac1.
authors.affiliation: Institute of Pharmacology, Biochemical-Pharmacological Center (BPC), University of Marburg, 35032 Marburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Grikscheit
authors.affiliation: Institute of Pharmacology, Biochemical-Pharmacological Center (BPC), University of Marburg, 35032 Marburg, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Frank
authors.affiliation: Institute of Pharmacology, Biochemical-Pharmacological Center (BPC), University of Marburg, 35032 Marburg, Germany.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Pharmacology, Biochemical-Pharmacological Center (BPC), University of Marburg, 35032 Marburg, Germany robert.grosse@staff.uni-marburg.de.
authors.forename: Robert
authors.initials: R
authors.lastname: Grosse
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D022005:Adherens Junctions / Q000235:genetics / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D000080865:Formins; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; C476208:FMNL2 protein, human; D000080865:Formins; D011506:Proteins; C107953:RAC1 protein, human; D020830:rac1 GTP-Binding Protein