Ca2+ Microdomains in T-Lymphocytes
Early Ca2+ signaling is characterized by occurrence of Ca2+ microdomains formed by opening of single or clusters of Ca2+ channels, thereby initiating first signaling and subsequently activating global Ca2+ signaling mechanisms. However, only few data are available focusing on the first seconds and m...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fonc.2017.00073/full |
| _version_ | 1818051013414748160 |
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| author | Andreas H. Guse Insa M. A. Wolf |
| author_facet | Andreas H. Guse Insa M. A. Wolf |
| author_sort | Andreas H. Guse |
| collection | DOAJ |
| description | Early Ca2+ signaling is characterized by occurrence of Ca2+ microdomains formed by opening of single or clusters of Ca2+ channels, thereby initiating first signaling and subsequently activating global Ca2+ signaling mechanisms. However, only few data are available focusing on the first seconds and minutes of Ca2+ microdomain formation and related signaling pathways in activated T-lymphocytes. In this review, we condense current knowledge on Ca2+ microdomain formation in T-lymphocytes and early Ca2+ signaling, function of Ca2+ microdomains, and microdomain organization. Interestingly, considering the first seconds of T cell activation, a triphasic Ca2+ signal is becoming apparent: (i) initial Ca2+ microdomains occurring in the first second of T cell activation, (ii) amplification of Ca2+ microdomains by recruitment of further channels in the next 5–10 s, and (iii) a transition to global Ca2+ increase. Apparently, the second messenger nicotinic acid adenine dinucleotide phosphate is the first second messenger involved in initiation of Ca2+ microdomains. Ryanodine receptors type 1 act as initial Ca2+ release channels in CD4+ T-lymphocytes. Regarding the temporal correlation of Ca2+ microdomains with other molecular events of T cell activation, T cell receptor-dependent microdomain organization of signaling molecules Grb2 and Src homology [SH2] domain-containing leukocyte protein of 65 kDa was observed within the first 20 s. In addition, fast cytoskeletal changes are initiated. Furthermore, the involvement of additional Ca2+ channels and organelles, such as the Ca2+ buffering mitochondria, is discussed. Future research developments will comprise analysis of the causal relation between these temporally coordinated signaling events. Taken together, high-resolution Ca2+ imaging techniques applied to T cell activation in the past years paved the way to detailed molecular understanding of initial Ca2+ signaling mechanisms in non-excitable cells. |
| first_indexed | 2024-12-10T11:02:37Z |
| format | Article |
| id | doaj.art-9859c11d1e764d75a607827ae004085b |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-10T11:02:37Z |
| publishDate | 2017-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-9859c11d1e764d75a607827ae004085b2022-12-22T01:51:39ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2017-05-01710.3389/fonc.2017.00073260022Ca2+ Microdomains in T-LymphocytesAndreas H. Guse0Insa M. A. Wolf1The Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Centre Hamburg-Eppendorf, Hamburg, GermanyThe Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Centre Hamburg-Eppendorf, Hamburg, GermanyEarly Ca2+ signaling is characterized by occurrence of Ca2+ microdomains formed by opening of single or clusters of Ca2+ channels, thereby initiating first signaling and subsequently activating global Ca2+ signaling mechanisms. However, only few data are available focusing on the first seconds and minutes of Ca2+ microdomain formation and related signaling pathways in activated T-lymphocytes. In this review, we condense current knowledge on Ca2+ microdomain formation in T-lymphocytes and early Ca2+ signaling, function of Ca2+ microdomains, and microdomain organization. Interestingly, considering the first seconds of T cell activation, a triphasic Ca2+ signal is becoming apparent: (i) initial Ca2+ microdomains occurring in the first second of T cell activation, (ii) amplification of Ca2+ microdomains by recruitment of further channels in the next 5–10 s, and (iii) a transition to global Ca2+ increase. Apparently, the second messenger nicotinic acid adenine dinucleotide phosphate is the first second messenger involved in initiation of Ca2+ microdomains. Ryanodine receptors type 1 act as initial Ca2+ release channels in CD4+ T-lymphocytes. Regarding the temporal correlation of Ca2+ microdomains with other molecular events of T cell activation, T cell receptor-dependent microdomain organization of signaling molecules Grb2 and Src homology [SH2] domain-containing leukocyte protein of 65 kDa was observed within the first 20 s. In addition, fast cytoskeletal changes are initiated. Furthermore, the involvement of additional Ca2+ channels and organelles, such as the Ca2+ buffering mitochondria, is discussed. Future research developments will comprise analysis of the causal relation between these temporally coordinated signaling events. Taken together, high-resolution Ca2+ imaging techniques applied to T cell activation in the past years paved the way to detailed molecular understanding of initial Ca2+ signaling mechanisms in non-excitable cells.http://journal.frontiersin.org/article/10.3389/fonc.2017.00073/fullnicotinic acid adenine dinucleotide phosphateT cellsignal transductionlocal Ca2+ signalsryanodine receptors |
| spellingShingle | Andreas H. Guse Insa M. A. Wolf Ca2+ Microdomains in T-Lymphocytes Frontiers in Oncology nicotinic acid adenine dinucleotide phosphate T cell signal transduction local Ca2+ signals ryanodine receptors |
| title | Ca2+ Microdomains in T-Lymphocytes |
| title_full | Ca2+ Microdomains in T-Lymphocytes |
| title_fullStr | Ca2+ Microdomains in T-Lymphocytes |
| title_full_unstemmed | Ca2+ Microdomains in T-Lymphocytes |
| title_short | Ca2+ Microdomains in T-Lymphocytes |
| title_sort | ca2 microdomains in t lymphocytes |
| topic | nicotinic acid adenine dinucleotide phosphate T cell signal transduction local Ca2+ signals ryanodine receptors |
| url | http://journal.frontiersin.org/article/10.3389/fonc.2017.00073/full |
| work_keys_str_mv | AT andreashguse ca2microdomainsintlymphocytes AT insamawolf ca2microdomainsintlymphocytes |