Midbody Remnant Inheritance Is Regulated by the ESCRT Subunit CHMP4C
Javier Casares-Arias,
María Ujué González,
Alvaro San Paulo,
Leandro N. Ventimiglia,
Jessica B.A. Sadler,
David G. Miguez,
Leticia Labat-de-Hoz,
Armando Rubio-Ramos,
Laura Rangel,
Miguel Bernabé-Rubio,
Jaime Fernández-Barrera,
Isabel Correas,
Juan Martín-Serrano,
Miguel A. Alonso
Affiliations
Javier Casares-Arias
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, 28049 Madrid, Spain
María Ujué González
Instituto de Micro y Nanotecnología, Consejo Superior de Investigaciones Científicas, 28760 Madrid, Spain
Alvaro San Paulo
Instituto de Micro y Nanotecnología, Consejo Superior de Investigaciones Científicas, 28760 Madrid, Spain
Leandro N. Ventimiglia
Department of Infectious Diseases, Faculty of Life Sciences and Medicine, King's College London, London SE1 9RT, UK
Jessica B.A. Sadler
Department of Infectious Diseases, Faculty of Life Sciences and Medicine, King's College London, London SE1 9RT, UK
David G. Miguez
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, 28049 Madrid, Spain; Department of Condensed Matter Physics, Universidad Autónoma de Madrid, 28049 Madrid, Spain
Leticia Labat-de-Hoz
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, 28049 Madrid, Spain
Armando Rubio-Ramos
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, 28049 Madrid, Spain
Laura Rangel
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, 28049 Madrid, Spain; Department of Molecular Biology, Universidad Autónoma de Madrid, 28049 Madrid, Spain
Miguel Bernabé-Rubio
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, 28049 Madrid, Spain
Jaime Fernández-Barrera
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, 28049 Madrid, Spain
Isabel Correas
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, 28049 Madrid, Spain; Department of Molecular Biology, Universidad Autónoma de Madrid, 28049 Madrid, Spain
Juan Martín-Serrano
Department of Infectious Diseases, Faculty of Life Sciences and Medicine, King's College London, London SE1 9RT, UK
Miguel A. Alonso
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, 28049 Madrid, Spain; Corresponding author
Summary: The inheritance of the midbody remnant (MBR) breaks the symmetry of the two daughter cells, with functional consequences for lumen and primary cilium formation by polarized epithelial cells, and also for development and differentiation. However, despite its importance, neither the relationship between the plasma membrane and the inherited MBR nor the mechanism of MBR inheritance is well known. Here, the analysis by correlative light and ultra-high-resolution scanning electron microscopy reveals a membranous stalk that physically connects the MBR to the apical membrane of epithelial cells. The stalk, which derives from the uncleaved side of the midbody, concentrates the ESCRT machinery. The ESCRT CHMP4C subunit enables MBR inheritance, and its depletion dramatically reduces the percentage of ciliated cells. We demonstrate (1) that MBRs are physically connected to the plasma membrane, (2) how CHMP4C helps maintain the integrity of the connection, and (3) the functional importance of the connection.