Plasmolipin regulates basolateral-to-apical transcytosis of ICAM-1 and leukocyte adhesion in polarized hepatic epithelial cells

• Published in: Cellular and molecular life sciences : CMLS Vol. 79; no. 1; p. 61
• Main Authors: Cacho-Navas, Cristina, Reglero-Real, Natalia, Colás-Algora, Natalia, Barroso, Susana, de Rivas, Gema, Stamatakis, Kostantinos, Feito, Jorge, Andrés, Germán, Fresno, Manuel, Kremer, Leonor, Correas, Isabel, Alonso, Miguel A., Millán, Jaime
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.01.2022; Springer Nature B.V
• Subjects: Adhesion; Bile ducts; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell adhesion; Cell Adhesion - physiology; Cell Biology; Cell Line, Tumor; Depletion; Epithelial cells; Epithelial Cells - metabolism; Epithelium; Genetic modification; Genome editing; Hep G2 Cells; Hepatocytes - metabolism; Humans; Inflammation; Inflammatory response; Intercellular adhesion molecule 1; Intercellular Adhesion Molecule-1 - metabolism; Leukocytes; Life Sciences; Liver; Liver - metabolism; Localization; Lymphocytes; Lymphocytes T; Membranes; Molecular modelling; Myelin and Lymphocyte-Associated Proteolipid Proteins - genetics; Myelin and Lymphocyte-Associated Proteolipid Proteins - metabolism; Original; Original Article; Polarity; Proteins; Receptors; SNAP receptors; T-Lymphocytes - metabolism; Transcytosis - physiology; Apicobasal polarity; BioID; Lymphocyte adhesion; Hepatocyte; PLLP; Subapical compartment, bile canaliculus; ICAM-1; Transcytosis
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-021-04095-z

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.