title: ROCK1 and ROCK2 regulate epithelial polarisation and geometric cell shape.
abstract: BACKGROUND
  Cell-cell adhesion and contraction play an essential role in the maintenance of geometric shape and polarisation of epithelial cells. However, the molecular regulation of contraction during cell elongation leading to epithelial polarisation and acquisition of geometric cell shape is not clear.
  
  
  RESULTS
  Upon induction of cell-cell adhesion, we find that human keratinocytes acquire specific geometric shapes favouring hexagons, by re-modelling junction length/orientation and thus neighbour allocation. Acquisition of geometric shape correlates temporally with epithelial polarisation, as shown by an increase in lateral height. ROCK1 and ROCK2 are important regulators of myosin II contraction, but their specific role in epithelial cell shape has not been addressed. Depletion of ROCK proteins interferes with the correct proportion of hexagonal cell shapes and full elongation of lateral domain. Interestingly, ROCK proteins are not essential for maintenance of circumferential thin bundles, the main contractile epithelial F-actin pool. Instead, ROCK1 or ROCK2 regulates thin bundle contraction and positioning along the lateral domain, an important event for the stabilisation of the elongating lateral domain. Mechanistically, E-cadherin clustering specifically leads to ROCK1/ROCK2-dependent inactivation of myosin phosphatase and phosphorylation of myosin regulatory light chain. These events correlate temporally with the increase in lateral height and thin bundle compaction towards junctions.
  
  
  CONCLUSIONS
  We conclude that ROCK proteins are necessary for acquisition of elongated and geometric cell shape, two key events for epithelial differentiation.
authors.affiliation: Faculty of Medicine, Molecular Medicine Section, National Heart and Lung Institute, Imperial College of London, London, UK.
authors.forename: Ruba
authors.initials: R
authors.lastname: Kalaji
authors.forename: Ann P
authors.initials: AP
authors.lastname: Wheeler
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Erasmus
authors.forename: Sang Y
authors.initials: SY
authors.lastname: Lee
authors.forename: Robert G
authors.initials: RG
authors.lastname: Endres
authors.forename: Louise P
authors.initials: LP
authors.lastname: Cramer
authors.forename: Vania M M
authors.initials: VM
authors.lastname: Braga
mesh_terms: D000199:Actins / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation; D016764:Cell Polarity / Q000502:physiology; D048430:Cell Shape / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D009024:Morphogenesis; D018994:Myosin Light Chains / Q000378:metabolism; D024462:Myosin Type II / Q000378:metabolism; D043263:Myosin-Light-Chain Phosphatase / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D000199:Actins; D015820:Cadherins; D018994:Myosin Light Chains; C515851:ROCK1 protein, human; C515852:ROCK2 protein, human; D054460:rho-Associated Kinases; D043263:Myosin-Light-Chain Phosphatase; D024462:Myosin Type II