eLife (Apr 2024)

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

  • Cristina Cacho-Navas,
  • Carmen López-Pujante,
  • Natalia Reglero-Real,
  • Natalia Colás-Algora,
  • Ana Cuervo,
  • Jose Javier Conesa,
  • Susana Barroso,
  • Gema de Rivas,
  • Sergio Ciordia,
  • Alberto Paradela,
  • Gianluca D'Agostino,
  • Carlo Manzo,
  • Jorge Feito,
  • Germán Andrés,
  • Francisca Molina-Jiménez,
  • Pedro Majano,
  • Isabel Correas,
  • José-Maria Carazo,
  • Sussan Nourshargh,
  • Meritxell Huch,
  • Jaime Millán

DOI
https://doi.org/10.7554/eLife.89261
Journal volume & issue
Vol. 12

Abstract

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Epithelial intercellular adhesion molecule (ICAM)-1 is apically polarized, interacts with, and guides leukocytes across epithelial barriers. Polarized hepatic epithelia organize their apical membrane domain into bile canaliculi and ducts, which are not accessible to circulating immune cells but that nevertheless confine most of ICAM-1. Here, by analyzing ICAM-1_KO human hepatic cells, liver organoids from ICAM-1_KO mice and rescue-of-function experiments, we show that ICAM-1 regulates epithelial apicobasal polarity in a leukocyte adhesion-independent manner. ICAM-1 signals to an actomyosin network at the base of canalicular microvilli, thereby controlling the dynamics and size of bile canalicular-like structures. We identified the scaffolding protein EBP50/NHERF1/SLC9A3R1, which connects membrane proteins with the underlying actin cytoskeleton, in the proximity interactome of ICAM-1. EBP50 and ICAM-1 form nano-scale domains that overlap in microvilli, from which ICAM-1 regulates EBP50 nano-organization. Indeed, EBP50 expression is required for ICAM-1-mediated control of BC morphogenesis and actomyosin. Our findings indicate that ICAM-1 regulates the dynamics of epithelial apical membrane domains beyond its role as a heterotypic cell–cell adhesion molecule and reveal potential therapeutic strategies for preserving epithelial architecture during inflammatory stress.

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