CaT1 Contributes to the Stores-operated Calcium Current in Jurkat T-lymphocytes

Cui, Jie; Bian, Jin-Song; Kagan, Anna; McDonald, Thomas V.

doi:10.1074/jbc.m205870200

Cited by 81 publications

(64 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is possible that no single Trp family protein alone forms the I CRAC channel, rather that there is a heteromultimeric channel formed from an assemblage of various Trp proteins. In support of this Cui et al (10) found that Jurkat T lymphocytes express both TrpV1 and TrpV5 (ECaC1) in addition to TrpV6 and suggested that TrpV5 contributed to the I CRAC current. Furthermore, Philipp et al (12) isolated a series of random mutants of Jurkat T cells with defects in TCR-dependent Ca 2ϩ entry.…”

supporting

confidence: 50%

“…Mammalian homologues of the Drosophila Trp proteins have been reported to be expressed in Jurkat T lymphocytes (7,8). The TrpV family member TrpV6 (CaT1) is the strongest contender for the I CRAC channel (9,10) although this has been disputed (11). It is possible that no single Trp family protein alone forms the I CRAC channel, rather that there is a heteromultimeric channel formed from an assemblage of various Trp proteins.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Non-voltage-gated L-type Ca2+ Channels in Human T Cells

Stokes¹,

Gordon²,

Grafton

2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

In T lymphocytes, engagement of the antigen receptor leads to a biphasic Ca 2؉ flux consisting of a mobilization of Ca 2؉ from intracellular stores followed by a lower but sustained elevation that is dependent on extracellular Ca 2؉ . The prolonged Ca 2؉ flux is required for activation of transcription factors and for subsequent activation of the T cell. Ca 2؉ influx requires as yet unidentified Ca 2؉ channels, which potentially play a role in T cell activation. Here we present evidence that human T cells express a non-voltage-gated Ca 2؉ channel related to L-type voltage-gated Ca 2؉ channels. Drugs that block classical L-type channels inhibited the initial phase of the antigen receptor-induced Ca 2؉ flux and could also inhibit the sustained phase of the Ca 2؉ signal suggesting a role for the L-type Ca 2؉ channel in antigen receptor signaling. T cells expressed transcripts for the ␣ 1 1.2 and ␣ 1 1.3 pore-forming subunits of L-type voltage-gated Ca 2؉ channels and transcripts for all four known ␤-subunits including several potential new splice variants. Jurkat T leukemia cells expressed a small amount of full-length ␣ 1 1.2 protein but the dominant form was a truncated protein identical in size to a truncated ␣ 1 1.2 protein known to be expressed in B lymphocytes. They further expressed a truncated form of the ␣ 1 1.3 subunit and auxiliary ␤1-and ␤3-subunit proteins. Our data strongly suggest that functional but non-voltage-gated L-type Ca 2؉ channels are expressed at the plasma membrane in T cells and play a role in the antigen receptor-mediated Ca 2؉ flux in these cells.

show abstract

supporting

confidence: 50%

mentioning

confidence: 99%

Non-voltage-gated L-type Ca2+ Channels in Human T Cells

Stokes¹,

Gordon²,

Grafton

2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…It was shown that the enzyme hydrolyzes and activates the TRPV5 channel conducting K ϩ (52) and hydrolyzes steroid ␤-glucuronides (10). Channels belonging to the TRPV family are present in the T cell membranes and might be involved in the immune cells' activation (53). Thus, possible lack of their activation related to decreased or even nullified Klotho activity could be one of the causes of impaired activation of the T cells both in healthy aged people as well as in RA patients.…”

Section: Discussionmentioning

confidence: 99%

Klotho—a Common Link in Physiological and Rheumatoid Arthritis-Related Aging of Human CD4+ Lymphocytes

Witkowski

Soroczyńska-Cybula

Bryl

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

Human CD4+ T lymphocytes undergo aging-related changes leading to decreased immunity to infections and neoplasms, and to increased frequency of autoimmune diseases including rheumatoid arthritis (RA). Certain changes, observed in the CD4+ cells of RA patients, resemble those observed during physiological aging, but occur at earlier age. Underlying cellular mechanism(s) of these similarities are so far largely unknown. Here we show that KLOTHO, a β-glucuronidase gene whose activity changes are associated with aging phenotype, is down-regulated at the mRNA, protein, and enzymatic (β-glucuronidase) activity levels both in the healthy elderly and especially in RA CD4+ lymphocytes. Although the exact role of Klotho activity for CD4+ cell function is unknown, we propose here that it might be involved in anti-inflammatory processes occurring in the young and healthy individuals, but reduced in both healthy elderly and RA patients. To support this hypothesis, we show here that the reduction of Klotho expression and activity in both elderly and patients’ lymphocytes occurs in concert with the down-regulation of T cell costimulatory molecule CD28, the latter known to be dependent on increased levels of TNF-α. Thus, a common mechanism of KLOTHO down-regulation, but executed at various times in life, may underlie both physiological and disease-related T cell aging. Klotho activity might become a target of anti-RA drug development as well as a tool to help increase the immune system efficiency in the elderly.

show abstract

“…However, it still remains possible that CRAC channels are formed with a heterologous combination of different trp proteins (see (Venkatachalam et al, 2002) for a recent review). Involvement of CaT1 (TRPV6) in such a combination has been strongly suggested in Jurkat T cells (Cui et al, 2002;Yue et al, 2001).…”

Section: Ca 2+ Influxmentioning

confidence: 99%

Ca²⁺ signals and T lymphocytes “New mechanisms and functions in Ca²⁺ signalling”

Randriamampita

Trautmann

2004

Biology of the Cell

View full text Add to dashboard Cite

Interaction between a T cell and an antigen-presenting cell leads to the rapid formation of an immunological synapse allowing antigen detection by the T cell and the development of an immune response. Antigen detection triggers various cellular responses including a modest but sustained T cell Ca 2+ increase. In this review are discussed a series of related questions. What are the various molecular events by which a T cell Ca 2+ response can be triggered in the immunological synapse by a very small amount of antigen ? How is Ca 2+ released from intracellular stores and how can these stores remain empty for hours ? Through which channels does Ca 2+ influx takes place, and how is Ca 2+ influx coupled to Ca 2+ release from intracellular stores ? What are the main immediate and indirect cellular targets of the Ca 2+ increase ?

show abstract

CaT1 Contributes to the Stores-operated Calcium Current in Jurkat T-lymphocytes

Abstract: T-lymphocyte activation requires sustained

Cited by 81 publications

References 45 publications

Non-voltage-gated L-type Ca2+ Channels in Human T Cells

Non-voltage-gated L-type Ca2+ Channels in Human T Cells

Klotho—a Common Link in Physiological and Rheumatoid Arthritis-Related Aging of Human CD4+ Lymphocytes

Ca²⁺ signals and T lymphocytes “New mechanisms and functions in Ca²⁺ signalling”

Contact Info

Product

Resources

About

CaT1 Contributes to the Stores-operated Calcium Current in Jurkat T-lymphocytes

Abstract: T-lymphocyte activation requires sustained

Cited by 81 publications

References 45 publications

Non-voltage-gated L-type Ca2+ Channels in Human T Cells

Non-voltage-gated L-type Ca2+ Channels in Human T Cells

Klotho—a Common Link in Physiological and Rheumatoid Arthritis-Related Aging of Human CD4+ Lymphocytes

Ca2+ signals and T lymphocytes “New mechanisms and functions in Ca2+ signalling”

Contact Info

Product

Resources

About

Ca²⁺ signals and T lymphocytes “New mechanisms and functions in Ca²⁺ signalling”