Regulation of monocarboxylic acid transporter-1 by cAMP dependent vesicular trafficking in brain microvascular endothelial cells.

In this study, a detailed characterization of Monocarboxylic Acid Transporter-1 (Mct1) in cytoplasmic vesicles of cultured rat brain microvascular endothelial cells shows them to be a diverse population of endosomes intrinsic to the regulation of the transporter by a brief 25 to 30 minute exposure t...

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Autores principales:	Amy L Uhernik, Lun Li, Nathan LaVoy, Micah J Velasquez, Jeffrey P Smith
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ede53dc4c28c4fe7bff673cc283474f1
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spelling	oai:doaj.org-article:ede53dc4c28c4fe7bff673cc283474f12021-11-18T08:37:32ZRegulation of monocarboxylic acid transporter-1 by cAMP dependent vesicular trafficking in brain microvascular endothelial cells.1932-620310.1371/journal.pone.0085957https://doaj.org/article/ede53dc4c28c4fe7bff673cc283474f12014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24454947/?tool=EBIhttps://doaj.org/toc/1932-6203In this study, a detailed characterization of Monocarboxylic Acid Transporter-1 (Mct1) in cytoplasmic vesicles of cultured rat brain microvascular endothelial cells shows them to be a diverse population of endosomes intrinsic to the regulation of the transporter by a brief 25 to 30 minute exposure to the membrane permeant cAMP analog, 8Br-cAMP. The vesicles are heterogeneous in size, mobility, internal pH, and co-localize with discreet markers of particular types of endosomes including early endosomes, clathrin coated vesicles, caveolar vesicles, trans-golgi, and lysosomes. The vesicular localization of Mct1 was not dependent on its N or C termini, however, the size and pH of Mct1 vesicles was increased by deletion of either terminus demonstrating a role for the termini in vesicular trafficking of Mct1. Using a novel BCECF-AM based assay developed in this study, 8Br-cAMP was shown to decrease the pH of Mct1 vesicles after 25 minutes. This result and method were confirmed in experiments with a ratiometric pH-sensitive EGFP-mCherry dual tagged Mct1 construct. Overall, the results indicate that cAMP signaling reduces the functionality of Mct1 in cerebrovascular endothelial cells by facilitating its entry into a highly dynamic vesicular trafficking pathway that appears to lead to the transporter's trafficking to autophagosomes and lysosomes.Amy L UhernikLun LiNathan LaVoyMicah J VelasquezJeffrey P SmithPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 1, p e85957 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Amy L Uhernik Lun Li Nathan LaVoy Micah J Velasquez Jeffrey P Smith Regulation of monocarboxylic acid transporter-1 by cAMP dependent vesicular trafficking in brain microvascular endothelial cells.
description	In this study, a detailed characterization of Monocarboxylic Acid Transporter-1 (Mct1) in cytoplasmic vesicles of cultured rat brain microvascular endothelial cells shows them to be a diverse population of endosomes intrinsic to the regulation of the transporter by a brief 25 to 30 minute exposure to the membrane permeant cAMP analog, 8Br-cAMP. The vesicles are heterogeneous in size, mobility, internal pH, and co-localize with discreet markers of particular types of endosomes including early endosomes, clathrin coated vesicles, caveolar vesicles, trans-golgi, and lysosomes. The vesicular localization of Mct1 was not dependent on its N or C termini, however, the size and pH of Mct1 vesicles was increased by deletion of either terminus demonstrating a role for the termini in vesicular trafficking of Mct1. Using a novel BCECF-AM based assay developed in this study, 8Br-cAMP was shown to decrease the pH of Mct1 vesicles after 25 minutes. This result and method were confirmed in experiments with a ratiometric pH-sensitive EGFP-mCherry dual tagged Mct1 construct. Overall, the results indicate that cAMP signaling reduces the functionality of Mct1 in cerebrovascular endothelial cells by facilitating its entry into a highly dynamic vesicular trafficking pathway that appears to lead to the transporter's trafficking to autophagosomes and lysosomes.
format	article
author	Amy L Uhernik Lun Li Nathan LaVoy Micah J Velasquez Jeffrey P Smith
author_facet	Amy L Uhernik Lun Li Nathan LaVoy Micah J Velasquez Jeffrey P Smith
author_sort	Amy L Uhernik
title	Regulation of monocarboxylic acid transporter-1 by cAMP dependent vesicular trafficking in brain microvascular endothelial cells.
title_short	Regulation of monocarboxylic acid transporter-1 by cAMP dependent vesicular trafficking in brain microvascular endothelial cells.
title_full	Regulation of monocarboxylic acid transporter-1 by cAMP dependent vesicular trafficking in brain microvascular endothelial cells.
title_fullStr	Regulation of monocarboxylic acid transporter-1 by cAMP dependent vesicular trafficking in brain microvascular endothelial cells.
title_full_unstemmed	Regulation of monocarboxylic acid transporter-1 by cAMP dependent vesicular trafficking in brain microvascular endothelial cells.
title_sort	regulation of monocarboxylic acid transporter-1 by camp dependent vesicular trafficking in brain microvascular endothelial cells.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/ede53dc4c28c4fe7bff673cc283474f1
work_keys_str_mv	AT amyluhernik regulationofmonocarboxylicacidtransporter1bycampdependentvesiculartraffickinginbrainmicrovascularendothelialcells AT lunli regulationofmonocarboxylicacidtransporter1bycampdependentvesiculartraffickinginbrainmicrovascularendothelialcells AT nathanlavoy regulationofmonocarboxylicacidtransporter1bycampdependentvesiculartraffickinginbrainmicrovascularendothelialcells AT micahjvelasquez regulationofmonocarboxylicacidtransporter1bycampdependentvesiculartraffickinginbrainmicrovascularendothelialcells AT jeffreypsmith regulationofmonocarboxylicacidtransporter1bycampdependentvesiculartraffickinginbrainmicrovascularendothelialcells
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Regulation of monocarboxylic acid transporter-1 by cAMP dependent vesicular trafficking in brain microvascular endothelial cells.

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