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

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...

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Detalles Bibliográficos
Autores: Cacho Navas, Cristina, López Pujante, Carmen, Reglero Real, Natalia, Colás Algora, Natalia, Cuervo, Ana, Conesa, Jose Javier, Barroso, Susana, de Rivas, Gema, Ciordia, Sergio, Paradela, Alberto, D'Agostino, Gianluca, Manzo, Carlo, Feito, Jorge, Andrés, Germán, Molina Jiménez, Francisca, Majano Rodríguez, Pedro Lorenzo, Correas, Isabel, Carazo, José Maria, Nourshargh, Sussan, Huch, Meritxell, Millán, Jaime
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/118973
Acceso en línea:https://hdl.handle.net/20.500.14352/118973
Access Level:acceso abierto
Palabra clave:576.3
577.1
612.35
Biología molecular (Biología)
Biología celular (Biología)
Bioquímica (Biología)
Fisiología
2415 Biología Molecular
2407 Biología Celular
2403 Bioquímica
2401.04 Citología Animal
32 Ciencias Médicas
Descripción
Sumario: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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