RT Journal Article
T1 ICAM-1 nanoclusters regulate hepatic epithelial cell polarity by leukocyte adhesion-independent control of apical actomyosin
A1 Cacho Navas, Cristina
A1 López Pujante, Carmen
A1 Reglero Real, Natalia
A1 Colás Algora, Natalia
A1 Cuervo, Ana
A1 Conesa, Jose Javier
A1 Barroso, Susana
A1 de Rivas, Gema
A1 Ciordia, Sergio
A1 Paradela, Alberto
A1 D'Agostino, Gianluca
A1 Manzo, Carlo
A1 Feito, Jorge
A1 Andrés, Germán
A1 Molina Jiménez, Francisca
A1 Majano Rodríguez, Pedro Lorenzo
A1 Correas, Isabel
A1 Carazo, José Maria
A1 Nourshargh, Sussan
A1 Huch, Meritxell
A1 Millán, Jaime
AB 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.
PB eLife Sciences Publications
SN 2050-084X
YR 2024
FD 2024
LK https://hdl.handle.net/20.500.14352/118973
UL https://hdl.handle.net/20.500.14352/118973
LA eng
NO Cacho-Navas, C., López-Pujante, C., Reglero-Real, N., Colás-Algora, N., Cuervo, A., Conesa, J. J., Barroso, S., De Rivas, G., Ciordia, S., Paradela, A., D’Agostino, G., Manzo, C., Feito, J., Andrés, G., Molina-Jiménez, F., Majano, P., Correas, I., Carazo, J.-M., Nourshargh, S., … Millán, J. (2024). ICAM-1 nanoclusters regulate hepatic epithelial cell polarity by leukocyte adhesion-independent control of apical actomyosin. eLife, 12, RP89261. https://doi.org/10.7554/eLife.89261.3
NO Financiación: Agencia Estatal de Investigación (PID2020-119881RB-I00), Comunidad de Madrid (P2022/BMD-7232 TomoXliver2), Comunidad de Madrid (IND2019/BMD-17139), Agencia Estatal de Investigación (PID2021-125386NB-I00), Marie Skłodowska-Curie Actions (608765), Agencia Estatal de Investigación (PID2022-137552OA-I00), Agencia Estatal de Investigación (RYC2021-031221-I), European Commission (Regulation EU 2020/2094), Fondo Europeo de Desarrollo Regional (PID2021-125386NB-I00), Ministry of Economy and Competitiveness (FPI fellowship), Ministry of Education, Culture and Sports (FPU fellowship), Fundación Jiménez Díaz University Hospital Health Research Institute (Endocornea Convenio Colaboración CSIC)
NO Ministerio de Ciencia, Innovación y Universidades (España)
NO Comunidad de Madrid
NO European Commission
NO Ministerio de Economía y Competitividad (España)
NO Ministerio de Educación, Cultura y Deporte (España)
NO Fundación Jiménez Díaz
DS Docta Complutense
RD 6 abr 2025