title: PAR-4/LKB1 mobilizes nonmuscle myosin through anillin to regulate C. elegans embryonic polarization and cytokinesis.
abstract: BACKGROUND
  The serine/threonine kinase LKB1 regulates cell growth and polarity in metazoans, and loss of LKB1 function is implicated in the development of some epithelial cancers. Despite its fundamental role, the mechanism by which LKB1 regulates polarity establishment and/or maintenance is unclear. In the present study, we use the nematode C. elegans to investigate the role of the LKB1 ortholog PAR-4 in actomyosin contractility, a cellular process essential for polarity establishment and cell division in the early embryo.
  
  
  RESULTS
  Using high-resolution time-lapse imaging of GFP-tagged nonmuscle myosin II (NMY-2), we found that par-4 mutations reduce actomyosin contractility during polarity establishment, leading to the mispositioning of anterior PAR proteins and to defects in contractile ring ingression during cytokinesis. Fluorescence recovery after photobleaching analysis revealed that the mobility of a cortical population of NMY-2 was reduced in par-4 mutants. Interestingly, the contractility defects of par-4 mutants depend on the reciprocal activity of ANI-1 and ANI-2, two C. elegans homologs of the actin cytoskeletal scaffold protein anillin.
  
  
  CONCLUSIONS
  Because loss of PAR-4 promoted inappropriate accumulation of ANI-2 at the cell cortex, we propose that PAR-4 controls C. elegans embryonic polarity by regulating the activity of anillin family scaffold proteins, thus enabling turnover of cortical myosin and efficient actomyosin contractility. This work provides the first description of a cellular mechanism by which PAR-4/LKB1 mediates cell polarization.
authors.affiliation: Institute of Research in Immunology and Cancer, Université de Montréal, Montréal, H3C 3J7 Québec, Canada. worm.machine@gmail.com
authors.forename: Nicolas T
authors.initials: NT
authors.lastname: Chartier
authors.forename: Diana P
authors.initials: DP
authors.lastname: Salazar Ospina
authors.forename: Laura
authors.initials: L
authors.lastname: Benkemoun
authors.forename: Mirjam
authors.initials: M
authors.lastname: Mayer
authors.forename: Stephan W
authors.initials: SW
authors.lastname: Grill
authors.forename: Amy S
authors.initials: AS
authors.lastname: Maddox
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Labbé
mesh_terms: D000205:Actomyosin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D016764:Cell Polarity; D048749:Cytokinesis / Q000502:physiology*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases
chemical_list: C502567:ANI-2 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D008840:Microfilament Proteins; C480837:NMY-2 protein, C elegans; D000205:Actomyosin; C097238:PAR-3 protein, C elegans; D017346:Protein Serine-Threonine Kinases; D018995:Myosin Heavy Chains