ICAM-1 nanoclusters regulate hepatic epithelial cell polarity by leukocyte adhesion-independent control of apical actomyosin

  1. Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Cantoblanco, Madrid, Spain
  2. William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
  3. Centro Nacional de Biotecnología, CSIC, Cantoblanco, Madrid, Spain
  4. Facultat de Ciències, Tecnologia i Enginyeries, Universitat de Vic – Universitat Central de Catalunya (UVic-UCC), Vic, Spain
  5. Servicio de Anatomía Patológica, Hospital Universitario de Salamanca, Salamanca, Spain
  6. Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany

Peer review process

Not revised: This Reviewed Preprint includes the authors’ original preprint (without revision), an eLife assessment, and public reviews.

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Editors

  • Reviewing Editor
    Pramod Mistry
    Yale University, New Haven, United States of America
  • Senior Editor
    Pramod Mistry
    Yale University, New Haven, United States of America

Joint Public Review:

In this study, Cacho-Navas et al. describe the role of ICAM-1 expressed on the apical membrane of bile canaliculi and its function to control the bile canaliculi (BCs) homeostasis. This is a previously unrecognized function of this protein in hepatocytes. The same authors have previously shown that basolateral ICAM-1 plays a role in controlling lymphocyte adhesion to hepatocytes during inflammation and that this interaction is responsible for the loss of polarity of hepatocytes during disease states.

This new study shows that ICAM-1 is mainly localized in the apical domain of the BC and in association with EBP-50, communicates with the subapical acto-myosin ring to regulate the size and morphology of the BC. They used the well-known immortal cell line of liver cells (HepG2) in which they deleted ICAM-1 gene by CRISPR-Cas9 editing and hepatic organoids derived from WT and ICAM-1-KO mice. alternating KO as well as rescue experiments. They show that in the absence of apical ICAM-1, the BC become dilated.

The data sufficiently support the conclusions of the study.

  1. Howard Hughes Medical Institute
  2. Wellcome Trust
  3. Max-Planck-Gesellschaft
  4. Knut and Alice Wallenberg Foundation