title: Distinct subdomain organization and molecular composition of a tight junction with adherens junction features.
abstract: Most polarized epithelia constrain solute diffusion between luminal and interstitial compartments using tight junctions and generate mechanical strength using adherens junctions. These intercellular junctions are typically portrayed as incongruent macromolecular complexes with distinct protein components. Herein, we delineate the molecular composition and subdomain architecture of an intercellular junction between sensory and non-sensory cells of the inner ear. In this junction, claudins partition into claudin-14 and claudin-9/6 subdomains that are distinguishable by strand morphology, which contrasts with in vitro data that most claudins co-assemble into heteromeric strands. Surprisingly, canonical adherens junction proteins (p120ctn, alpha- and beta-catenins) colocalize with the claudin-9/6 subdomain and recruit a dense cytoskeletal network. We also find that catenins colocalize with claudin-9 and claudin-6, but not claudin-14, in a heterologous system. Together, our data demonstrate that canonical tight junction and adherens junction proteins can be recruited to a single junction in which claudins partition into subdomains and form a novel hybrid tight junction with adherens junction organization.
authors.affiliation: Laboratory of Cellular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Fabio D
authors.initials: FD
authors.lastname: Nunes
authors.forename: Lanier N
authors.initials: LN
authors.lastname: Lopez
authors.forename: Harrison W
authors.initials: HW
authors.lastname: Lin
authors.forename: Caroline
authors.initials: C
authors.lastname: Davies
authors.forename: Ricardo B
authors.initials: RB
authors.lastname: Azevedo
authors.forename: Alexander
authors.initials: A
authors.lastname: Gow
authors.forename: Bechara
authors.initials: B
authors.lastname: Kachar
mesh_terms: D000199:Actins / Q000378:metabolism; D022005:Adherens Junctions / Q000737:chemistry*; D000818:Animals; D001485:Basement Membrane / Q000166:cytology; D019556:COS Cells; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002522:Chlorocebus aethiops; D057167:Claudins; D007758:Ear, Inner / Q000166:cytology; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000166:cytology; D018072:Hair Cells, Auditory, Outer / Q000166:cytology; D007365:Intercellular Junctions / Q000737:chemistry; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D051381:Rats; D019108:Tight Junctions / Q000737:chemistry*; D003689:Vestibular Nucleus, Lateral / Q000166:cytology; D051176:beta Catenin / Q000378:metabolism; D000095002:Delta Catenin
chemical_list: D000199:Actins; D051177:Catenins; D015815:Cell Adhesion Molecules; D057167:Claudins; C515808:Cldn9 protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; D051176:beta Catenin; C122101:claudin 6; C422064:claudin 14; D000095002:Delta Catenin