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

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,...

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Autores: 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/378762
Acceso en línea:http://hdl.handle.net/10261/378762
Access Level:acceso abierto
Palabra clave:Apicobasal polarity
BioID
Hepatocyte
ICAM-1
Lymphocyte adhesion
PLLP
Subapical compartment, bile canaliculus
Transcytosis.
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spelling Plasmolipin regulates basolateral-to-apical transcytosis of ICAM-1 and leukocyte adhesion in polarized hepatic epithelial cellsCacho-Navas, CristinaReglero-Real, NataliaColás-Algora, NataliaBarroso, Susanade Rivas, GemaStamatakis, KostantinosFeito, JorgeAndrés, GermánFresno, ManuelKremer, LeonorCorreas, IsabelAlonso, Miguel A.Millán, JaimeApicobasal polarityBioIDHepatocyteICAM-1Lymphocyte adhesionPLLPSubapical compartment, bile canaliculusTranscytosis.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.The work was supported by grants SAF2017-88187-R and PID2020-119881RB-I00 from AEI (to J.M.) and S2017/BMD-3817 TomoXliver (to J.M., J.M.C and I.C.) and IND2019/BMD-17139 (to J.M.) from Comunidad de Madrid. S.B.F is supported by Endocornea, convenio colaboración CSIC, funded by Instituto de Investigación Fundación Jiménez Díaz. C.C-N. is a recipient of FPI fellowships from MINECO. N.C-A. is a recipient of an FPU fellowship from MECD. N.R-R is additionally supported by funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007–2013) under REA grant agreement n°608765. Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature.Birkhäuser VerlagSpringer NatureAgencia Estatal de Investigación (España)Comunidad de MadridHospital Universitario Fundación Jiménez DíazMinisterio de Economía y Competitividad (España)European CommissionConsejo Superior de Investigaciones Científicas (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2025202520222025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/378762reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2017-88187-Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-119881RB-I00http://dx.doi.org/10.1007/s00018-021-04095-zSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3787622026-05-22T06:33:51Z
dc.title.none.fl_str_mv Plasmolipin regulates basolateral-to-apical transcytosis of ICAM-1 and leukocyte adhesion in polarized hepatic epithelial cells
title Plasmolipin regulates basolateral-to-apical transcytosis of ICAM-1 and leukocyte adhesion in polarized hepatic epithelial cells
spellingShingle Plasmolipin regulates basolateral-to-apical transcytosis of ICAM-1 and leukocyte adhesion in polarized hepatic epithelial cells
Cacho-Navas, Cristina
Apicobasal polarity
BioID
Hepatocyte
ICAM-1
Lymphocyte adhesion
PLLP
Subapical compartment, bile canaliculus
Transcytosis.
title_short Plasmolipin regulates basolateral-to-apical transcytosis of ICAM-1 and leukocyte adhesion in polarized hepatic epithelial cells
title_full Plasmolipin regulates basolateral-to-apical transcytosis of ICAM-1 and leukocyte adhesion in polarized hepatic epithelial cells
title_fullStr Plasmolipin regulates basolateral-to-apical transcytosis of ICAM-1 and leukocyte adhesion in polarized hepatic epithelial cells
title_full_unstemmed Plasmolipin regulates basolateral-to-apical transcytosis of ICAM-1 and leukocyte adhesion in polarized hepatic epithelial cells
title_sort Plasmolipin regulates basolateral-to-apical transcytosis of ICAM-1 and leukocyte adhesion in polarized hepatic epithelial cells
dc.creator.none.fl_str_mv 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
author Cacho-Navas, Cristina
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Agencia Estatal de Investigación (España)
Comunidad de Madrid
Hospital Universitario Fundación Jiménez Díaz
Ministerio de Economía y Competitividad (España)
European Commission
Consejo Superior de Investigaciones Científicas (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Apicobasal polarity
BioID
Hepatocyte
ICAM-1
Lymphocyte adhesion
PLLP
Subapical compartment, bile canaliculus
Transcytosis.
topic Apicobasal polarity
BioID
Hepatocyte
ICAM-1
Lymphocyte adhesion
PLLP
Subapical compartment, bile canaliculus
Transcytosis.
description 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.
publishDate 2022
dc.date.none.fl_str_mv 2022
2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/378762
url http://hdl.handle.net/10261/378762
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2017-88187-R
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-119881RB-I00
http://dx.doi.org/10.1007/s00018-021-04095-z
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Birkhäuser Verlag
Springer Nature
publisher.none.fl_str_mv Birkhäuser Verlag
Springer Nature
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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