AKAP350 Is Involved in the Development of Apical ‘‘Canalicular’’ Structures in Hepatic Cells HepG2

Autores
Mattaloni, Stella Maris; Kolobova, Elena; Favre, Cristian; Marinelli, Raul Alberto; Goldenring, James R.; Larocca, Maria Cecilia
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Hepatocytes are epithelial cells whose apical poles constitute the bile canaliculi. The establishment and maintenance of canalicular poles is a finely regulated process that dictates the efficiency of primary bile secretion. Protein kinase A (PKA) modulates this process at different levels. AKAP350 is an A-kinase anchoring protein that scaffolds protein complexes involved in modulating the dynamic structures of the Golgi apparatus and microtubule cytoskeleton, facilitating microtubule nucleation at this organelle. In this study, we evaluated whether AKAP350 is involved in the development of bile canaliculi-like structures in hepatocyte derived HepG2 cells. We found that AKAP350 recruits PKA to the centrosomes and Golgi apparatus in HepG2 cells. De-localization of AKAP350 from these organelles led to reduced apical cell polarization. A decrease in AKAP350 expression inhibited the formation of canalicular structures and impaired F-actin organization at canalicular poles. Furthermore, loss of AKAP350 expression led to diminished polarized expression of the p-glycoprotein (MDR1/ABCB1) at the apical ‘‘canalicular’’ membrane. AKAP350 knock down effects on canalicular structures formation and actin organization could be mimicked by inhibition of Golgi microtubule nucleation by depletion of CLIP associated proteins (CLASPs). Our data reveal that AKAP350 participates in mechanisms which determine the development of canalicular structures as well as accurate canalicular expression of distinct proteins and actin organization, and provide evidence on the involvement of Golgi microtubule nucleation in hepatocyte apical polarization.
Fil: Mattaloni, Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
Fil: Kolobova, Elena. Vanderbilt University School of Medicine; Estados Unidos
Fil: Favre, Cristian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
Fil: Marinelli, Raul Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
Fil: Goldenring, James R.. Vanderbilt University School of Medicine; Estados Unidos
Fil: Larocca, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
Materia
AKAP350
PKA
BILE CANALICULUS
CLASP
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/280939
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/280939
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling AKAP350 Is Involved in the Development of Apical ‘‘Canalicular’’ Structures in Hepatic Cells HepG2Mattaloni, Stella MarisKolobova, ElenaFavre, CristianMarinelli, Raul AlbertoGoldenring, James R.Larocca, Maria CeciliaAKAP350PKABILE CANALICULUSCLASPhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Hepatocytes are epithelial cells whose apical poles constitute the bile canaliculi. The establishment and maintenance of canalicular poles is a finely regulated process that dictates the efficiency of primary bile secretion. Protein kinase A (PKA) modulates this process at different levels. AKAP350 is an A-kinase anchoring protein that scaffolds protein complexes involved in modulating the dynamic structures of the Golgi apparatus and microtubule cytoskeleton, facilitating microtubule nucleation at this organelle. In this study, we evaluated whether AKAP350 is involved in the development of bile canaliculi-like structures in hepatocyte derived HepG2 cells. We found that AKAP350 recruits PKA to the centrosomes and Golgi apparatus in HepG2 cells. De-localization of AKAP350 from these organelles led to reduced apical cell polarization. A decrease in AKAP350 expression inhibited the formation of canalicular structures and impaired F-actin organization at canalicular poles. Furthermore, loss of AKAP350 expression led to diminished polarized expression of the p-glycoprotein (MDR1/ABCB1) at the apical ‘‘canalicular’’ membrane. AKAP350 knock down effects on canalicular structures formation and actin organization could be mimicked by inhibition of Golgi microtubule nucleation by depletion of CLIP associated proteins (CLASPs). Our data reveal that AKAP350 participates in mechanisms which determine the development of canalicular structures as well as accurate canalicular expression of distinct proteins and actin organization, and provide evidence on the involvement of Golgi microtubule nucleation in hepatocyte apical polarization.Fil: Mattaloni, Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; ArgentinaFil: Kolobova, Elena. Vanderbilt University School of Medicine; Estados UnidosFil: Favre, Cristian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; ArgentinaFil: Marinelli, Raul Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; ArgentinaFil: Goldenring, James R.. Vanderbilt University School of Medicine; Estados UnidosFil: Larocca, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; ArgentinaWiley-liss, div John Wiley & Sons Inc.2011-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/280939Mattaloni, Stella Maris; Kolobova, Elena; Favre, Cristian; Marinelli, Raul Alberto; Goldenring, James R.; et al.; AKAP350 Is Involved in the Development of Apical ‘‘Canalicular’’ Structures in Hepatic Cells HepG2; Wiley-liss, div John Wiley & Sons Inc.; Journal of Cellular Physiology; 226; 3-2011; 1-130021-9541CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1002/jcp.22713info:eu-repo/semantics/altIdentifier/doi/10.1002/jcp.22713info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-02-06T13:13:05Zoai:ri.conicet.gov.ar:11336/280939instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982026-02-06 13:13:05.665CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv AKAP350 Is Involved in the Development of Apical ‘‘Canalicular’’ Structures in Hepatic Cells HepG2
title AKAP350 Is Involved in the Development of Apical ‘‘Canalicular’’ Structures in Hepatic Cells HepG2
spellingShingle AKAP350 Is Involved in the Development of Apical ‘‘Canalicular’’ Structures in Hepatic Cells HepG2
Mattaloni, Stella Maris
AKAP350
PKA
BILE CANALICULUS
CLASP
title_short AKAP350 Is Involved in the Development of Apical ‘‘Canalicular’’ Structures in Hepatic Cells HepG2
title_full AKAP350 Is Involved in the Development of Apical ‘‘Canalicular’’ Structures in Hepatic Cells HepG2
title_fullStr AKAP350 Is Involved in the Development of Apical ‘‘Canalicular’’ Structures in Hepatic Cells HepG2
title_full_unstemmed AKAP350 Is Involved in the Development of Apical ‘‘Canalicular’’ Structures in Hepatic Cells HepG2
title_sort AKAP350 Is Involved in the Development of Apical ‘‘Canalicular’’ Structures in Hepatic Cells HepG2
dc.creator.none.fl_str_mv Mattaloni, Stella Maris
Kolobova, Elena
Favre, Cristian
Marinelli, Raul Alberto
Goldenring, James R.
Larocca, Maria Cecilia
author Mattaloni, Stella Maris
author_facet Mattaloni, Stella Maris
Kolobova, Elena
Favre, Cristian
Marinelli, Raul Alberto
Goldenring, James R.
Larocca, Maria Cecilia
author_role author
author2 Kolobova, Elena
Favre, Cristian
Marinelli, Raul Alberto
Goldenring, James R.
Larocca, Maria Cecilia
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv AKAP350
PKA
BILE CANALICULUS
CLASP
topic AKAP350
PKA
BILE CANALICULUS
CLASP
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Hepatocytes are epithelial cells whose apical poles constitute the bile canaliculi. The establishment and maintenance of canalicular poles is a finely regulated process that dictates the efficiency of primary bile secretion. Protein kinase A (PKA) modulates this process at different levels. AKAP350 is an A-kinase anchoring protein that scaffolds protein complexes involved in modulating the dynamic structures of the Golgi apparatus and microtubule cytoskeleton, facilitating microtubule nucleation at this organelle. In this study, we evaluated whether AKAP350 is involved in the development of bile canaliculi-like structures in hepatocyte derived HepG2 cells. We found that AKAP350 recruits PKA to the centrosomes and Golgi apparatus in HepG2 cells. De-localization of AKAP350 from these organelles led to reduced apical cell polarization. A decrease in AKAP350 expression inhibited the formation of canalicular structures and impaired F-actin organization at canalicular poles. Furthermore, loss of AKAP350 expression led to diminished polarized expression of the p-glycoprotein (MDR1/ABCB1) at the apical ‘‘canalicular’’ membrane. AKAP350 knock down effects on canalicular structures formation and actin organization could be mimicked by inhibition of Golgi microtubule nucleation by depletion of CLIP associated proteins (CLASPs). Our data reveal that AKAP350 participates in mechanisms which determine the development of canalicular structures as well as accurate canalicular expression of distinct proteins and actin organization, and provide evidence on the involvement of Golgi microtubule nucleation in hepatocyte apical polarization.
Fil: Mattaloni, Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
Fil: Kolobova, Elena. Vanderbilt University School of Medicine; Estados Unidos
Fil: Favre, Cristian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
Fil: Marinelli, Raul Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
Fil: Goldenring, James R.. Vanderbilt University School of Medicine; Estados Unidos
Fil: Larocca, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
description Hepatocytes are epithelial cells whose apical poles constitute the bile canaliculi. The establishment and maintenance of canalicular poles is a finely regulated process that dictates the efficiency of primary bile secretion. Protein kinase A (PKA) modulates this process at different levels. AKAP350 is an A-kinase anchoring protein that scaffolds protein complexes involved in modulating the dynamic structures of the Golgi apparatus and microtubule cytoskeleton, facilitating microtubule nucleation at this organelle. In this study, we evaluated whether AKAP350 is involved in the development of bile canaliculi-like structures in hepatocyte derived HepG2 cells. We found that AKAP350 recruits PKA to the centrosomes and Golgi apparatus in HepG2 cells. De-localization of AKAP350 from these organelles led to reduced apical cell polarization. A decrease in AKAP350 expression inhibited the formation of canalicular structures and impaired F-actin organization at canalicular poles. Furthermore, loss of AKAP350 expression led to diminished polarized expression of the p-glycoprotein (MDR1/ABCB1) at the apical ‘‘canalicular’’ membrane. AKAP350 knock down effects on canalicular structures formation and actin organization could be mimicked by inhibition of Golgi microtubule nucleation by depletion of CLIP associated proteins (CLASPs). Our data reveal that AKAP350 participates in mechanisms which determine the development of canalicular structures as well as accurate canalicular expression of distinct proteins and actin organization, and provide evidence on the involvement of Golgi microtubule nucleation in hepatocyte apical polarization.
publishDate 2011
dc.date.none.fl_str_mv 2011-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/280939
Mattaloni, Stella Maris; Kolobova, Elena; Favre, Cristian; Marinelli, Raul Alberto; Goldenring, James R.; et al.; AKAP350 Is Involved in the Development of Apical ‘‘Canalicular’’ Structures in Hepatic Cells HepG2; Wiley-liss, div John Wiley & Sons Inc.; Journal of Cellular Physiology; 226; 3-2011; 1-13
0021-9541
CONICET Digital
CONICET
url http://hdl.handle.net/11336/280939
identifier_str_mv Mattaloni, Stella Maris; Kolobova, Elena; Favre, Cristian; Marinelli, Raul Alberto; Goldenring, James R.; et al.; AKAP350 Is Involved in the Development of Apical ‘‘Canalicular’’ Structures in Hepatic Cells HepG2; Wiley-liss, div John Wiley & Sons Inc.; Journal of Cellular Physiology; 226; 3-2011; 1-13
0021-9541
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1002/jcp.22713
info:eu-repo/semantics/altIdentifier/doi/10.1002/jcp.22713
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley-liss, div John Wiley & Sons Inc.
publisher.none.fl_str_mv Wiley-liss, div John Wiley & Sons Inc.
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.106097

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