Plasmolipin regulates basolateral-to-apical transcytosis of ICAM-1 and leukocyte adhesion in polarized hepatic epithelial cells
EntityUAM. Departamento de Biología Molecular
10.1007/s00018-021-04095-zCellular and Molecular Life Sciences 79.1 (2022): 61
ISSN1420-682X (print); 1420-9071 (online)
ProjectGobierno de España. SAF2017-88187-R; Gobierno de España. PID2020-119881RB-I00; Comunidad de Madrid. S2017/BMD-3817/TomoXliver; Comunidad de Madrid. IND2019/BMD-17139; info:eu-repo/grantAgreement/EC/FP7/608765
SubjectsApicobasal polarity; BioID; Hepatocyte; ICAM-1; Lymphocyte adhesion; PLLP; Subapical compartment, bile canaliculus; Transcytosis; Biología y Biomedicina / Biología
Rights© The Author(s) 2022
Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.
Apical localization of Intercellular Adhesion Receptor (ICAM)-1 regulates the adhesion and guidance of leukocytes across polarized epithelial barriers. Here, we investigate the molecular mechanisms that determine ICAM-1 localization into apical membrane domains of polarized hepatic epithelial cells, and their effect on lymphocyte-hepatic epithelial cell interaction. We had previously shown that segregation of ICAM-1 into apical membrane domains, which form bile canaliculi and bile ducts in hepatic epithelial cells, requires basolateral-to-apical transcytosis. Searching for protein machinery potentially involved in ICAM-1 polarization we found that the SNARE-associated protein plasmolipin (PLLP) is expressed in the subapical compartment of hepatic epithelial cells in vitro and in vivo. BioID analysis of ICAM-1 revealed proximal interaction between this adhesion receptor and PLLP. ICAM-1 colocalized and interacted with PLLP during the transcytosis of the receptor. PLLP gene editing and silencing increased the basolateral localization and reduced the apical confinement of ICAM-1 without affecting apicobasal polarity of hepatic epithelial cells, indicating that ICAM-1 transcytosis is specifically impaired in the absence of PLLP. Importantly, PLLP depletion was sufficient to increase T-cell adhesion to hepatic epithelial cells. Such an increase depended on the epithelial cell polarity and ICAM-1 expression, showing that the epithelial transcytotic machinery regulates the adhesion of lymphocytes to polarized epithelial cells. Our findings strongly suggest that the polarized intracellular transport of adhesion receptors constitutes a new regulatory layer of the epithelial inflammatory response
Google Scholar:Cacho Navas, Cristina - Reglero Real, Natalia - Colás Algora, Natalia - Barroso, Susana - de Rivas, Gema - Stamatakis Andriani, Konstantinos - Feito, Jorge - Andrés, Germán - Fresno Escudero, Manuel - Kremer, Leonor - Correas Hornero, María Isabel - Alonso, Miguel Angel - Millán, Jaime
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