Immune Synapse Residency of Orai1 Alters Ca<sup>2+</sup> Response of T Cells

CRAC, which plays important role in Ca<sup>2+</sup>-dependent T-lymphocyte activation, is composed of the ER-resident STIM1 and the plasma membrane Orai1 pore-forming subunit. Both accumulate at the immunological synapse (IS) between a T cell and an antigen-presenting cell (APC). We hypo...

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Autores principales:	Orsolya Voros, György Panyi, Péter Hajdu
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Orai1 immunological synapse calcium signaling STIM1 SAP97 Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/524ec433210a453aa979554d90566f7e
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spelling	oai:doaj.org-article:524ec433210a453aa979554d90566f7e2021-11-11T16:58:34ZImmune Synapse Residency of Orai1 Alters Ca<sup>2+</sup> Response of T Cells10.3390/ijms2221115141422-00671661-6596https://doaj.org/article/524ec433210a453aa979554d90566f7e2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11514https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067CRAC, which plays important role in Ca<sup>2+</sup>-dependent T-lymphocyte activation, is composed of the ER-resident STIM1 and the plasma membrane Orai1 pore-forming subunit. Both accumulate at the immunological synapse (IS) between a T cell and an antigen-presenting cell (APC). We hypothesized that adapter/interacting proteins regulate Orai1 residence in the IS. We could show that mGFP-tagged Orai1-Full channels expressed in Jurkat cells had a biphasic IS-accumulation kinetics peaked at 15 min. To understand the background of Orai1 IS-redistribution we knocked down STIM1 and SAP97 (adaptor protein with a short IS-residency (15 min) and ability to bind Orai1 N-terminus): the mGFP-Orai1-Full channels kept on accumulating in the IS up to the 60th minute in the STIM1- and SAP97-lacking Jurkat cells. Deletion of Orai1 N terminus (mGFP-Orai1-Δ72) resulted in the same time course as described for STIM1/SAP97 knock-down cells. Ca<sup>2+</sup>-imaging of IS-engaged T-cells revealed that of Orai1 residency modifies the Ca<sup>2+</sup>-response: cells expressing mGFP-Orai1-Δ72 construct or mGFP-Orai1-Full in SAP-97 knock-down cells showed higher number of Ca<sup>2+</sup>-oscillation up to the 90th minute after IS formation. Overall, these data suggest that SAP97 may contribute to the short-lived IS-residency of Orai1 and binding of STIM1 to Orai1 N-terminus is necessary for SAP97-Orai1 interaction.Orsolya VorosGyörgy PanyiPéter HajduMDPI AGarticleOrai1immunological synapsecalcium signalingSTIM1SAP97Biology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11514, p 11514 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Orai1 immunological synapse calcium signaling STIM1 SAP97 Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	Orai1 immunological synapse calcium signaling STIM1 SAP97 Biology (General) QH301-705.5 Chemistry QD1-999 Orsolya Voros György Panyi Péter Hajdu Immune Synapse Residency of Orai1 Alters Ca<sup>2+</sup> Response of T Cells
description	CRAC, which plays important role in Ca<sup>2+</sup>-dependent T-lymphocyte activation, is composed of the ER-resident STIM1 and the plasma membrane Orai1 pore-forming subunit. Both accumulate at the immunological synapse (IS) between a T cell and an antigen-presenting cell (APC). We hypothesized that adapter/interacting proteins regulate Orai1 residence in the IS. We could show that mGFP-tagged Orai1-Full channels expressed in Jurkat cells had a biphasic IS-accumulation kinetics peaked at 15 min. To understand the background of Orai1 IS-redistribution we knocked down STIM1 and SAP97 (adaptor protein with a short IS-residency (15 min) and ability to bind Orai1 N-terminus): the mGFP-Orai1-Full channels kept on accumulating in the IS up to the 60th minute in the STIM1- and SAP97-lacking Jurkat cells. Deletion of Orai1 N terminus (mGFP-Orai1-Δ72) resulted in the same time course as described for STIM1/SAP97 knock-down cells. Ca<sup>2+</sup>-imaging of IS-engaged T-cells revealed that of Orai1 residency modifies the Ca<sup>2+</sup>-response: cells expressing mGFP-Orai1-Δ72 construct or mGFP-Orai1-Full in SAP-97 knock-down cells showed higher number of Ca<sup>2+</sup>-oscillation up to the 90th minute after IS formation. Overall, these data suggest that SAP97 may contribute to the short-lived IS-residency of Orai1 and binding of STIM1 to Orai1 N-terminus is necessary for SAP97-Orai1 interaction.
format	article
author	Orsolya Voros György Panyi Péter Hajdu
author_facet	Orsolya Voros György Panyi Péter Hajdu
author_sort	Orsolya Voros
title	Immune Synapse Residency of Orai1 Alters Ca<sup>2+</sup> Response of T Cells
title_short	Immune Synapse Residency of Orai1 Alters Ca<sup>2+</sup> Response of T Cells
title_full	Immune Synapse Residency of Orai1 Alters Ca<sup>2+</sup> Response of T Cells
title_fullStr	Immune Synapse Residency of Orai1 Alters Ca<sup>2+</sup> Response of T Cells
title_full_unstemmed	Immune Synapse Residency of Orai1 Alters Ca<sup>2+</sup> Response of T Cells
title_sort	immune synapse residency of orai1 alters ca<sup>2+</sup> response of t cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/524ec433210a453aa979554d90566f7e
work_keys_str_mv	AT orsolyavoros immunesynapseresidencyoforai1alterscasup2supresponseoftcells AT gyorgypanyi immunesynapseresidencyoforai1alterscasup2supresponseoftcells AT peterhajdu immunesynapseresidencyoforai1alterscasup2supresponseoftcells
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Immune Synapse Residency of Orai1 Alters Ca<sup>2+</sup> Response of T Cells

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