title: NMII forms a contractile transcellular sarcomeric network to regulate apical cell junctions and tissue geometry.
abstract: Nonmuscle myosin II (NMII) is thought to be the master integrator of force within epithelial apical junctions, mediating epithelial tissue morphogenesis and tensional homeostasis. Mutations in NMII are associated with a number of diseases due to failures in cell-cell adhesion. However, the organization and the precise mechanism by which NMII generates and responds to tension along the intercellular junctional line are still not known. We discovered that periodic assemblies of bipolar NMII filaments interlace with perijunctional actin and α-actinin to form a continuous belt of muscle-like sarcomeric units (∼400-600 nm) around each epithelial cell. Remarkably, the sarcomeres of adjacent cells are precisely paired across the junctional line, forming an integrated, transcellular contractile network. The contraction/relaxation of paired sarcomeres concomitantly impacts changes in apical cell shape and tissue geometry. We show differential distribution of NMII isoforms across heterotypic junctions and evidence for compensation between isoforms. Our results provide a model for how NMII force generation is effected along the junctional perimeter of each cell and communicated across neighboring cells in the epithelial organization. The sarcomeric network also provides a well-defined target to investigate the multiple roles of NMII in junctional homeostasis as well as in development and disease.
authors.affiliation: Laboratory of Cell Structure and Dynamics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Seham
authors.initials: S
authors.lastname: Ebrahim
authors.forename: Tomoki
authors.initials: T
authors.lastname: Fujita
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Millis
authors.forename: Elliott
authors.initials: E
authors.lastname: Kozin
authors.forename: Xuefei
authors.initials: X
authors.lastname: Ma
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Kawamoto
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Baird
authors.forename: Michael
authors.initials: M
authors.lastname: Davidson
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Yonemura
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hisa
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Conti
authors.forename: Robert S
authors.initials: RS
authors.lastname: Adelstein
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Sakaguchi
authors.forename: Bechara
authors.initials: B
authors.lastname: Kachar
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000185:Actinin / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D006576:Heterocyclic Compounds, 4 or More Rings / Q000378:metabolism; D007365:Intercellular Junctions / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D024462:Myosin Type II / Q000235:genetics / Q000378:metabolism*; D009925:Organ of Corti / Q000378:metabolism*; D051381:Rats
chemical_list: D000199:Actins; D006576:Heterocyclic Compounds, 4 or More Rings; C483905:Myh14 protein, mouse; D000185:Actinin; C472645:blebbistatin; D024462:Myosin Type II; D018995:Myosin Heavy Chains
references.citation: Blood. 2012 Jan 5;119(1):238-50
references.pmid: 21908426
references.citation: Nat Genet. 2000 Sep;26(1):103-5
references.pmid: 10973259
references.citation: Cell Mol Life Sci. 2013 Jan;70(1):1-21
references.pmid: 22565821
references.citation: Cytoskeleton (Hoboken). 2011 Mar;68(3):150-6
references.pmid: 21225702
references.citation: J Cell Biol. 1995 Nov;131(4):989-1002
references.pmid: 7490299
references.citation: J Cell Sci. 2011 Feb 15;124(Pt 4):548-55
references.pmid: 21245199
references.citation: J Cell Biol. 2005 Dec 19;171(6):939-45
references.pmid: 16365161
references.citation: Dev Biol. 1967 May;15(5):432-50
references.pmid: 6032487
references.citation: Cell Motil Cytoskeleton. 1989;12(3):150-6
references.pmid: 2653646
references.citation: J Cell Biol. 1975 Oct;67(1):72-92
references.pmid: 240861
references.citation: Science. 2003 Mar 14;299(5613):1743-7
references.pmid: 12637748
references.citation: J Cell Sci. 2005 Nov 15;118(Pt 22):5191-203
references.pmid: 16249236
references.citation: Am J Hum Genet. 2000 Nov;67(5):1121-8
references.pmid: 11023810
references.citation: J Cell Sci. 2007 Oct 15;120(Pt 20):3491-9
references.pmid: 17928305
references.citation: J Cell Sci. 2008 Jan 1;121(Pt 1):11-8
references.pmid: 18096687
references.citation: Development. 2009 Jun;136(12):1977-86
references.pmid: 19439495
references.citation: Nat Cell Biol. 2011 Apr;13(4):371-81
references.pmid: 21423177
references.citation: Curr Opin Struct Biol. 1997 Apr;7(2):247-57
references.pmid: 9094325
references.citation: Biochem Soc Trans. 2011 Oct;39(5):1131-5
references.pmid: 21936777
references.citation: J Physiol. 1966 May;184(1):170-92
references.pmid: 5921536
references.citation: Nature. 2004 Jun 10;429(6992):667-71
references.pmid: 15190355
references.citation: Semin Cell Dev Biol. 2008 Dec;19(6):511-9
references.pmid: 18793739
references.citation: J Biol Chem. 2004 Oct 1;279(40):41263-6
references.pmid: 15292239
references.citation: Dev Cell. 2009 Nov;17(5):736-43
references.pmid: 19879198
references.citation: Dis Esophagus. 2012 Jul;25(5):427-36
references.pmid: 21951916
references.citation: Science. 1990 Jul 27;249(4967):406-8
references.pmid: 2377894
references.citation: PLoS Biol. 2012 Feb;10(2):e1001256
references.pmid: 22346733
references.citation: Biophys J. 2006 Nov 15;91(10):3907-20
references.pmid: 16920834