Activated α2-Macroglobulin regulates LRP1 levels at the plasma membrane through the activation of a Rab10-dependent exocytic pathway in retinal Müller glial cells

Autores
Jaldín Fincati, Javier Roberto; Actis Dato, Virginia; Díaz, Nicolás Maximiliano; Sánchez, María C.; Barcelona, Pablo Federico; Chiabrando, Gustavo Alberto
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Activated α2-macroglobulin (α2M*) and its receptor, low-density lipoprotein receptor-related protein 1 (LRP1), have been linked to proliferative retinal diseases. In Müller glial cells (MGCs), the α2M*/LRP1 interaction induces cell signaling, cell migration, and extracellular matrix remodeling, processes closely associated with proliferative disorders. However, the mechanism whereby α2M* and LRP1 participate in the aforementioned pathologies remains incompletely elucidated. Here, we investigate whether α2M* regulates both the intracellular distribution and sorting of LRP1 to the plasma membrane (PM) and how this regulation is involved in the cell migration of MGCs. Using a human Müller glial-derived cell line, MIO-M1, we demonstrate that the α2M*/LRP1 complex is internalized and rapidly reaches early endosomes. Afterward, α2M* is routed to degradative compartments, while LRP1 is accumulated at the PM through a Rab10-dependent exocytic pathway regulated by PI3K/Akt. Interestingly, Rab10 knockdown reduces both LRP1 accumulation at the PM and cell migration of MIO-M1 cells induced by α2M*. Given the importance of MGCs in the maintenance of retinal homeostasis, unravelling this molecular mechanism can potentially provide new therapeutic targets for the treatment of proliferative retinopathies.
Fil: Jaldín Fincati, Javier Roberto. University of Toronto; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba; Argentina
Fil: Actis Dato, Virginia. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Díaz, Nicolás Maximiliano. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina
Fil: Sánchez, María C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba; Argentina
Fil: Barcelona, Pablo Federico. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Chiabrando, Gustavo Alberto. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Materia
ENDOCYTOSIS
EXOCYTOSIS
MACROGLOBULIN
MEMBRANES
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:11336/129168
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/129168
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Activated α2-Macroglobulin regulates LRP1 levels at the plasma membrane through the activation of a Rab10-dependent exocytic pathway in retinal Müller glial cellsJaldín Fincati, Javier RobertoActis Dato, VirginiaDíaz, Nicolás MaximilianoSánchez, María C.Barcelona, Pablo FedericoChiabrando, Gustavo AlbertoENDOCYTOSISEXOCYTOSISMACROGLOBULINMEMBRANEShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Activated α2-macroglobulin (α2M*) and its receptor, low-density lipoprotein receptor-related protein 1 (LRP1), have been linked to proliferative retinal diseases. In Müller glial cells (MGCs), the α2M*/LRP1 interaction induces cell signaling, cell migration, and extracellular matrix remodeling, processes closely associated with proliferative disorders. However, the mechanism whereby α2M* and LRP1 participate in the aforementioned pathologies remains incompletely elucidated. Here, we investigate whether α2M* regulates both the intracellular distribution and sorting of LRP1 to the plasma membrane (PM) and how this regulation is involved in the cell migration of MGCs. Using a human Müller glial-derived cell line, MIO-M1, we demonstrate that the α2M*/LRP1 complex is internalized and rapidly reaches early endosomes. Afterward, α2M* is routed to degradative compartments, while LRP1 is accumulated at the PM through a Rab10-dependent exocytic pathway regulated by PI3K/Akt. Interestingly, Rab10 knockdown reduces both LRP1 accumulation at the PM and cell migration of MIO-M1 cells induced by α2M*. Given the importance of MGCs in the maintenance of retinal homeostasis, unravelling this molecular mechanism can potentially provide new therapeutic targets for the treatment of proliferative retinopathies.Fil: Jaldín Fincati, Javier Roberto. University of Toronto; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba; ArgentinaFil: Actis Dato, Virginia. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Díaz, Nicolás Maximiliano. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Sánchez, María C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba; ArgentinaFil: Barcelona, Pablo Federico. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Chiabrando, Gustavo Alberto. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaNature Publishing Group2019-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/129168Jaldín Fincati, Javier Roberto; Actis Dato, Virginia; Díaz, Nicolás Maximiliano; Sánchez, María C.; Barcelona, Pablo Federico; et al.; Activated α2-Macroglobulin regulates LRP1 levels at the plasma membrane through the activation of a Rab10-dependent exocytic pathway in retinal Müller glial cells; Nature Publishing Group; Scientific Reports; 9; 1; 12-2019; 1-122045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-019-49072-6info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:05:06Zoai:ri.conicet.gov.ar:11336/129168instacron: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:34982025-09-10 13:05:06.908CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Activated α2-Macroglobulin regulates LRP1 levels at the plasma membrane through the activation of a Rab10-dependent exocytic pathway in retinal Müller glial cells
title Activated α2-Macroglobulin regulates LRP1 levels at the plasma membrane through the activation of a Rab10-dependent exocytic pathway in retinal Müller glial cells
spellingShingle Activated α2-Macroglobulin regulates LRP1 levels at the plasma membrane through the activation of a Rab10-dependent exocytic pathway in retinal Müller glial cells
Jaldín Fincati, Javier Roberto
ENDOCYTOSIS
EXOCYTOSIS
MACROGLOBULIN
MEMBRANES
title_short Activated α2-Macroglobulin regulates LRP1 levels at the plasma membrane through the activation of a Rab10-dependent exocytic pathway in retinal Müller glial cells
title_full Activated α2-Macroglobulin regulates LRP1 levels at the plasma membrane through the activation of a Rab10-dependent exocytic pathway in retinal Müller glial cells
title_fullStr Activated α2-Macroglobulin regulates LRP1 levels at the plasma membrane through the activation of a Rab10-dependent exocytic pathway in retinal Müller glial cells
title_full_unstemmed Activated α2-Macroglobulin regulates LRP1 levels at the plasma membrane through the activation of a Rab10-dependent exocytic pathway in retinal Müller glial cells
title_sort Activated α2-Macroglobulin regulates LRP1 levels at the plasma membrane through the activation of a Rab10-dependent exocytic pathway in retinal Müller glial cells
dc.creator.none.fl_str_mv Jaldín Fincati, Javier Roberto
Actis Dato, Virginia
Díaz, Nicolás Maximiliano
Sánchez, María C.
Barcelona, Pablo Federico
Chiabrando, Gustavo Alberto
author Jaldín Fincati, Javier Roberto
author_facet Jaldín Fincati, Javier Roberto
Actis Dato, Virginia
Díaz, Nicolás Maximiliano
Sánchez, María C.
Barcelona, Pablo Federico
Chiabrando, Gustavo Alberto
author_role author
author2 Actis Dato, Virginia
Díaz, Nicolás Maximiliano
Sánchez, María C.
Barcelona, Pablo Federico
Chiabrando, Gustavo Alberto
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv ENDOCYTOSIS
EXOCYTOSIS
MACROGLOBULIN
MEMBRANES
topic ENDOCYTOSIS
EXOCYTOSIS
MACROGLOBULIN
MEMBRANES
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Activated α2-macroglobulin (α2M*) and its receptor, low-density lipoprotein receptor-related protein 1 (LRP1), have been linked to proliferative retinal diseases. In Müller glial cells (MGCs), the α2M*/LRP1 interaction induces cell signaling, cell migration, and extracellular matrix remodeling, processes closely associated with proliferative disorders. However, the mechanism whereby α2M* and LRP1 participate in the aforementioned pathologies remains incompletely elucidated. Here, we investigate whether α2M* regulates both the intracellular distribution and sorting of LRP1 to the plasma membrane (PM) and how this regulation is involved in the cell migration of MGCs. Using a human Müller glial-derived cell line, MIO-M1, we demonstrate that the α2M*/LRP1 complex is internalized and rapidly reaches early endosomes. Afterward, α2M* is routed to degradative compartments, while LRP1 is accumulated at the PM through a Rab10-dependent exocytic pathway regulated by PI3K/Akt. Interestingly, Rab10 knockdown reduces both LRP1 accumulation at the PM and cell migration of MIO-M1 cells induced by α2M*. Given the importance of MGCs in the maintenance of retinal homeostasis, unravelling this molecular mechanism can potentially provide new therapeutic targets for the treatment of proliferative retinopathies.
Fil: Jaldín Fincati, Javier Roberto. University of Toronto; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba; Argentina
Fil: Actis Dato, Virginia. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Díaz, Nicolás Maximiliano. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina
Fil: Sánchez, María C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba; Argentina
Fil: Barcelona, Pablo Federico. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Chiabrando, Gustavo Alberto. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
description Activated α2-macroglobulin (α2M*) and its receptor, low-density lipoprotein receptor-related protein 1 (LRP1), have been linked to proliferative retinal diseases. In Müller glial cells (MGCs), the α2M*/LRP1 interaction induces cell signaling, cell migration, and extracellular matrix remodeling, processes closely associated with proliferative disorders. However, the mechanism whereby α2M* and LRP1 participate in the aforementioned pathologies remains incompletely elucidated. Here, we investigate whether α2M* regulates both the intracellular distribution and sorting of LRP1 to the plasma membrane (PM) and how this regulation is involved in the cell migration of MGCs. Using a human Müller glial-derived cell line, MIO-M1, we demonstrate that the α2M*/LRP1 complex is internalized and rapidly reaches early endosomes. Afterward, α2M* is routed to degradative compartments, while LRP1 is accumulated at the PM through a Rab10-dependent exocytic pathway regulated by PI3K/Akt. Interestingly, Rab10 knockdown reduces both LRP1 accumulation at the PM and cell migration of MIO-M1 cells induced by α2M*. Given the importance of MGCs in the maintenance of retinal homeostasis, unravelling this molecular mechanism can potentially provide new therapeutic targets for the treatment of proliferative retinopathies.
publishDate 2019
dc.date.none.fl_str_mv 2019-12
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/11336/129168
Jaldín Fincati, Javier Roberto; Actis Dato, Virginia; Díaz, Nicolás Maximiliano; Sánchez, María C.; Barcelona, Pablo Federico; et al.; Activated α2-Macroglobulin regulates LRP1 levels at the plasma membrane through the activation of a Rab10-dependent exocytic pathway in retinal Müller glial cells; Nature Publishing Group; Scientific Reports; 9; 1; 12-2019; 1-12
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/129168
identifier_str_mv Jaldín Fincati, Javier Roberto; Actis Dato, Virginia; Díaz, Nicolás Maximiliano; Sánchez, María C.; Barcelona, Pablo Federico; et al.; Activated α2-Macroglobulin regulates LRP1 levels at the plasma membrane through the activation of a Rab10-dependent exocytic pathway in retinal Müller glial cells; Nature Publishing Group; Scientific Reports; 9; 1; 12-2019; 1-12
2045-2322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-019-49072-6
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
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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 12.993085

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