Evidence of in vivo exogen protein uptake by red blood cells: a putative therapeutic concept

Autores
Hertz, Laura; Flormann, Daniel; Birnbaumer, Lutz; Wagner, Christian; Laschke, Matthias W.; Kaestner, Lars
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
For some molecular players in red blood cells (RBCs), the functional indications and molecular evidence are discrepant. One such protein is transient receptor potential channel of canonical subfamily, member 6 (TRPC6). Transcriptome analysis of reticulocytes revealed the presence of TRPC6 in mouse RBCs and its absence in human RBCs. We transfused TRPC6 knockout RBCs into wild-type mice and performed functional tests. We observed the "rescue" of TRPC6 within 10 days; however, the "rescue" was slower in splenectomized mice. The latter finding led us to mimic the mechanical challenge with the cantilever of an atomic force microscope and simultaneously carry out imaging by confocal (3D) microscopy. We observed the strong interaction of RBCs with the opposed surface at around 200 pN and the formation of tethers. The results of both the transfusion experiments and the atomic force spectroscopy suggest mechanically stimulated protein transfer to RBCs as a protein source in the absence of the translational machinery. This protein transfer mechanism has the potential to be utilized in therapeutic contexts, especially for hereditary diseases involving RBCs, such as hereditary xerocytosis or Gárdos channelopathy.
Fil: Hertz, Laura. Universitat Saarland; Alemania
Fil: Flormann, Daniel. Universitat Saarland; Alemania
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Wagner, Christian. Universitat Saarland; Alemania
Fil: Laschke, Matthias W.. Universitat Saarland; Alemania
Fil: Kaestner, Lars. Universitat Saarland; Alemania
Materia
TRPC6
RED BLOOD CELLS
CHANNELOPATIES
CALCIUM
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:11336/255853
Acceder
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network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Evidence of in vivo exogen protein uptake by red blood cells: a putative therapeutic conceptHertz, LauraFlormann, DanielBirnbaumer, LutzWagner, ChristianLaschke, Matthias W.Kaestner, LarsTRPC6RED BLOOD CELLSCHANNELOPATIESCALCIUMhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1For some molecular players in red blood cells (RBCs), the functional indications and molecular evidence are discrepant. One such protein is transient receptor potential channel of canonical subfamily, member 6 (TRPC6). Transcriptome analysis of reticulocytes revealed the presence of TRPC6 in mouse RBCs and its absence in human RBCs. We transfused TRPC6 knockout RBCs into wild-type mice and performed functional tests. We observed the "rescue" of TRPC6 within 10 days; however, the "rescue" was slower in splenectomized mice. The latter finding led us to mimic the mechanical challenge with the cantilever of an atomic force microscope and simultaneously carry out imaging by confocal (3D) microscopy. We observed the strong interaction of RBCs with the opposed surface at around 200 pN and the formation of tethers. The results of both the transfusion experiments and the atomic force spectroscopy suggest mechanically stimulated protein transfer to RBCs as a protein source in the absence of the translational machinery. This protein transfer mechanism has the potential to be utilized in therapeutic contexts, especially for hereditary diseases involving RBCs, such as hereditary xerocytosis or Gárdos channelopathy.Fil: Hertz, Laura. Universitat Saarland; AlemaniaFil: Flormann, Daniel. Universitat Saarland; AlemaniaFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Wagner, Christian. Universitat Saarland; AlemaniaFil: Laschke, Matthias W.. Universitat Saarland; AlemaniaFil: Kaestner, Lars. Universitat Saarland; AlemaniaAmerican Society of Hematology2023-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/255853Hertz, Laura; Flormann, Daniel; Birnbaumer, Lutz; Wagner, Christian; Laschke, Matthias W.; et al.; Evidence of in vivo exogen protein uptake by red blood cells: a putative therapeutic concept; American Society of Hematology; Blood Advances; 7; 6; 3-2023; 1033-10392473-95292473-9537CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://ashpublications.org/bloodadvances/article/7/6/1033/493565/Evidence-of-in-vivo-exogen-protein-uptake-by-redinfo:eu-repo/semantics/altIdentifier/doi/10.1182/bloodadvances.2022008404info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-05T10:31:35Zoai:ri.conicet.gov.ar:11336/255853instacron: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:34982025-11-05 10:31:35.333CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Evidence of in vivo exogen protein uptake by red blood cells: a putative therapeutic concept
title Evidence of in vivo exogen protein uptake by red blood cells: a putative therapeutic concept
spellingShingle Evidence of in vivo exogen protein uptake by red blood cells: a putative therapeutic concept
Hertz, Laura
TRPC6
RED BLOOD CELLS
CHANNELOPATIES
CALCIUM
title_short Evidence of in vivo exogen protein uptake by red blood cells: a putative therapeutic concept
title_full Evidence of in vivo exogen protein uptake by red blood cells: a putative therapeutic concept
title_fullStr Evidence of in vivo exogen protein uptake by red blood cells: a putative therapeutic concept
title_full_unstemmed Evidence of in vivo exogen protein uptake by red blood cells: a putative therapeutic concept
title_sort Evidence of in vivo exogen protein uptake by red blood cells: a putative therapeutic concept
dc.creator.none.fl_str_mv Hertz, Laura
Flormann, Daniel
Birnbaumer, Lutz
Wagner, Christian
Laschke, Matthias W.
Kaestner, Lars
author Hertz, Laura
author_facet Hertz, Laura
Flormann, Daniel
Birnbaumer, Lutz
Wagner, Christian
Laschke, Matthias W.
Kaestner, Lars
author_role author
author2 Flormann, Daniel
Birnbaumer, Lutz
Wagner, Christian
Laschke, Matthias W.
Kaestner, Lars
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv TRPC6
RED BLOOD CELLS
CHANNELOPATIES
CALCIUM
topic TRPC6
RED BLOOD CELLS
CHANNELOPATIES
CALCIUM
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv For some molecular players in red blood cells (RBCs), the functional indications and molecular evidence are discrepant. One such protein is transient receptor potential channel of canonical subfamily, member 6 (TRPC6). Transcriptome analysis of reticulocytes revealed the presence of TRPC6 in mouse RBCs and its absence in human RBCs. We transfused TRPC6 knockout RBCs into wild-type mice and performed functional tests. We observed the "rescue" of TRPC6 within 10 days; however, the "rescue" was slower in splenectomized mice. The latter finding led us to mimic the mechanical challenge with the cantilever of an atomic force microscope and simultaneously carry out imaging by confocal (3D) microscopy. We observed the strong interaction of RBCs with the opposed surface at around 200 pN and the formation of tethers. The results of both the transfusion experiments and the atomic force spectroscopy suggest mechanically stimulated protein transfer to RBCs as a protein source in the absence of the translational machinery. This protein transfer mechanism has the potential to be utilized in therapeutic contexts, especially for hereditary diseases involving RBCs, such as hereditary xerocytosis or Gárdos channelopathy.
Fil: Hertz, Laura. Universitat Saarland; Alemania
Fil: Flormann, Daniel. Universitat Saarland; Alemania
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Wagner, Christian. Universitat Saarland; Alemania
Fil: Laschke, Matthias W.. Universitat Saarland; Alemania
Fil: Kaestner, Lars. Universitat Saarland; Alemania
description For some molecular players in red blood cells (RBCs), the functional indications and molecular evidence are discrepant. One such protein is transient receptor potential channel of canonical subfamily, member 6 (TRPC6). Transcriptome analysis of reticulocytes revealed the presence of TRPC6 in mouse RBCs and its absence in human RBCs. We transfused TRPC6 knockout RBCs into wild-type mice and performed functional tests. We observed the "rescue" of TRPC6 within 10 days; however, the "rescue" was slower in splenectomized mice. The latter finding led us to mimic the mechanical challenge with the cantilever of an atomic force microscope and simultaneously carry out imaging by confocal (3D) microscopy. We observed the strong interaction of RBCs with the opposed surface at around 200 pN and the formation of tethers. The results of both the transfusion experiments and the atomic force spectroscopy suggest mechanically stimulated protein transfer to RBCs as a protein source in the absence of the translational machinery. This protein transfer mechanism has the potential to be utilized in therapeutic contexts, especially for hereditary diseases involving RBCs, such as hereditary xerocytosis or Gárdos channelopathy.
publishDate 2023
dc.date.none.fl_str_mv 2023-03
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/11336/255853
Hertz, Laura; Flormann, Daniel; Birnbaumer, Lutz; Wagner, Christian; Laschke, Matthias W.; et al.; Evidence of in vivo exogen protein uptake by red blood cells: a putative therapeutic concept; American Society of Hematology; Blood Advances; 7; 6; 3-2023; 1033-1039
2473-9529
2473-9537
CONICET Digital
CONICET
url http://hdl.handle.net/11336/255853
identifier_str_mv Hertz, Laura; Flormann, Daniel; Birnbaumer, Lutz; Wagner, Christian; Laschke, Matthias W.; et al.; Evidence of in vivo exogen protein uptake by red blood cells: a putative therapeutic concept; American Society of Hematology; Blood Advances; 7; 6; 3-2023; 1033-1039
2473-9529
2473-9537
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://ashpublications.org/bloodadvances/article/7/6/1033/493565/Evidence-of-in-vivo-exogen-protein-uptake-by-red
info:eu-repo/semantics/altIdentifier/doi/10.1182/bloodadvances.2022008404
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
dc.publisher.none.fl_str_mv American Society of Hematology
publisher.none.fl_str_mv American Society of Hematology
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
_version_ 1847977992872001536
score 13.087074

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