KCa3.1 and TRPM7 channels at the uropod regulate migration of activated human T cells.

The migration of T lymphocytes is an essential part of the adaptive immune response as T cells circulate around the body to carry out immune surveillance. During the migration process T cells polarize, forming a leading edge at the cell front and a uropod at the cell rear. Our interest was in studyi...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Zerrin Kuras, Yeo-Heung Yun, Ameet A Chimote, Lisa Neumeier, Laura Conforti
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6115844ae3d44e51b18f24cf2cc78111
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6115844ae3d44e51b18f24cf2cc78111
record_format	dspace
spelling	oai:doaj.org-article:6115844ae3d44e51b18f24cf2cc781112021-11-18T07:07:31ZKCa3.1 and TRPM7 channels at the uropod regulate migration of activated human T cells.1932-620310.1371/journal.pone.0043859https://doaj.org/article/6115844ae3d44e51b18f24cf2cc781112012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22952790/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The migration of T lymphocytes is an essential part of the adaptive immune response as T cells circulate around the body to carry out immune surveillance. During the migration process T cells polarize, forming a leading edge at the cell front and a uropod at the cell rear. Our interest was in studying the involvement of ion channels in the migration of activated human T lymphocytes as they modulate intracellular Ca(2+) levels. Ca(2+) is a key regulator of cellular motility. To this purpose, we created protein surfaces made of the bio-polymer PNMP and coated with ICAM-1, ligand of LFA-1. The LFA-1 and ICAM-1 interaction facilitates T cell movement from blood into tissues and it is critical in immune surveillance and inflammation. Activated human T lymphocytes polarized and migrated on ICAM-1 surfaces by random walk with a mean velocity of ∼6 µm/min. Confocal microscopy indicated that Kv1.3, CRAC, and TRPM4 channels positioned in the leading-edge, whereas KCa3.1 and TRPM7 channels accumulated in the uropod. The localization of KCa3.1 and TRPM7 at the uropod was associated with oscillations in intracellular Ca(2+) levels that we measured in this cell compartment. Further studies with blockers against Kv1.3 (ShK), KCa3.1 (TRAM-34), CRAC (SKF-96365), TRPM7 (2-APB), and TRPM4 (glibenclamide) indicated that blockade of KCa3.1 and TRPM7, and not Kv1.3, CRAC or TRPM4, inhibits the T cell migration. The involvement of TRPM7 in cell migration was confirmed with siRNAs against TRPM7. Downregulation of TRPM7 significantly reduced the number of migrating T cells and the mean velocity of the migrating T cells. These results indicate that KCa3.1 and TRPM7 selectively localize at the uropod of migrating T lymphocytes and are key components of the T cell migration machinery.Zerrin KurasYeo-Heung YunAmeet A ChimoteLisa NeumeierLaura ConfortiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 8, p e43859 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zerrin Kuras Yeo-Heung Yun Ameet A Chimote Lisa Neumeier Laura Conforti KCa3.1 and TRPM7 channels at the uropod regulate migration of activated human T cells.
description	The migration of T lymphocytes is an essential part of the adaptive immune response as T cells circulate around the body to carry out immune surveillance. During the migration process T cells polarize, forming a leading edge at the cell front and a uropod at the cell rear. Our interest was in studying the involvement of ion channels in the migration of activated human T lymphocytes as they modulate intracellular Ca(2+) levels. Ca(2+) is a key regulator of cellular motility. To this purpose, we created protein surfaces made of the bio-polymer PNMP and coated with ICAM-1, ligand of LFA-1. The LFA-1 and ICAM-1 interaction facilitates T cell movement from blood into tissues and it is critical in immune surveillance and inflammation. Activated human T lymphocytes polarized and migrated on ICAM-1 surfaces by random walk with a mean velocity of ∼6 µm/min. Confocal microscopy indicated that Kv1.3, CRAC, and TRPM4 channels positioned in the leading-edge, whereas KCa3.1 and TRPM7 channels accumulated in the uropod. The localization of KCa3.1 and TRPM7 at the uropod was associated with oscillations in intracellular Ca(2+) levels that we measured in this cell compartment. Further studies with blockers against Kv1.3 (ShK), KCa3.1 (TRAM-34), CRAC (SKF-96365), TRPM7 (2-APB), and TRPM4 (glibenclamide) indicated that blockade of KCa3.1 and TRPM7, and not Kv1.3, CRAC or TRPM4, inhibits the T cell migration. The involvement of TRPM7 in cell migration was confirmed with siRNAs against TRPM7. Downregulation of TRPM7 significantly reduced the number of migrating T cells and the mean velocity of the migrating T cells. These results indicate that KCa3.1 and TRPM7 selectively localize at the uropod of migrating T lymphocytes and are key components of the T cell migration machinery.
format	article
author	Zerrin Kuras Yeo-Heung Yun Ameet A Chimote Lisa Neumeier Laura Conforti
author_facet	Zerrin Kuras Yeo-Heung Yun Ameet A Chimote Lisa Neumeier Laura Conforti
author_sort	Zerrin Kuras
title	KCa3.1 and TRPM7 channels at the uropod regulate migration of activated human T cells.
title_short	KCa3.1 and TRPM7 channels at the uropod regulate migration of activated human T cells.
title_full	KCa3.1 and TRPM7 channels at the uropod regulate migration of activated human T cells.
title_fullStr	KCa3.1 and TRPM7 channels at the uropod regulate migration of activated human T cells.
title_full_unstemmed	KCa3.1 and TRPM7 channels at the uropod regulate migration of activated human T cells.
title_sort	kca3.1 and trpm7 channels at the uropod regulate migration of activated human t cells.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/6115844ae3d44e51b18f24cf2cc78111
work_keys_str_mv	AT zerrinkuras kca31andtrpm7channelsattheuropodregulatemigrationofactivatedhumantcells AT yeoheungyun kca31andtrpm7channelsattheuropodregulatemigrationofactivatedhumantcells AT ameetachimote kca31andtrpm7channelsattheuropodregulatemigrationofactivatedhumantcells AT lisaneumeier kca31andtrpm7channelsattheuropodregulatemigrationofactivatedhumantcells AT lauraconforti kca31andtrpm7channelsattheuropodregulatemigrationofactivatedhumantcells
_version_	1718423917830340608

KCa3.1 and TRPM7 channels at the uropod regulate migration of activated human T cells.

Ejemplares similares