The septate junction component bark beetle is required for Drosophila intestinal barrier function and homeostasis
Rachel A. Hodge,
Mirna Ghannam,
Emma Edmond,
Fernando de la Torre,
Cecilia D’Alterio,
Nida Hatice Kaya,
Martin Resnik-Docampo,
Tobias Reiff,
D. Leanne Jones
Affiliations
Rachel A. Hodge
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA
Mirna Ghannam
Institute of Genetics, Heinrich-Heine-University, Düsseldorf, Germany
Emma Edmond
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA
Fernando de la Torre
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA
Cecilia D’Alterio
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA
Nida Hatice Kaya
Institute of Genetics, Heinrich-Heine-University, Düsseldorf, Germany
Martin Resnik-Docampo
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA
Tobias Reiff
Institute of Genetics, Heinrich-Heine-University, Düsseldorf, Germany
D. Leanne Jones
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Medicine, Division of Geriatrics, University of California, San Francisco, San Francisco, CA 94143, USA; Bakar Aging Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA; Corresponding author
Summary: Age-related loss of intestinal barrier function has been documented across species, but the causes remain unknown. The intestinal barrier is maintained by tight junctions (TJs) in mammals and septate junctions (SJs) in insects. Specialized TJs/SJs, called tricellular junctions (TCJs), are located at the nexus of three adjacent cells, and we have shown that aging results in changes to TCJs in intestines of adult Drosophila melanogaster. We now demonstrate that localization of the TCJ protein bark beetle (Bark) decreases in aged flies. Depletion of bark from enterocytes in young flies led to hallmarks of intestinal aging and shortened lifespan, whereas depletion of bark in progenitor cells reduced Notch activity, biasing differentiation toward the secretory lineage. Our data implicate Bark in EC maturation and maintenance of intestinal barrier integrity. Understanding the assembly and maintenance of TCJs to ensure barrier integrity may lead to strategies to improve tissue integrity when function is compromised.
