TRESK potassium channel in human T lymphoblasts

Sánchez-Miguel, Dénison Selene; García-Dolores, Fernando; Flores-Márquez, María Rosa; Delgado‐Enciso, Iván; Pottosin, Igor; Dobrovinskaya, Oxana

doi:10.1016/j.bbrc.2013.02.115

Cited by 11 publications

(8 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The activity of K2P channels is practically independent of the membrane voltage; rather, they are regulated by a variety of metabolic and physical factors. First reports on the functional expression of TASK1 and 3 in T cells [ 195 ] and of TRESK in Jurkat leukemic T cells [ 196 , 197 ] in human models came relatively recently. Further on, TASK2 was found to be constitutively expressed in human T cells, but not in B or NK cells.…”

Section: Ion Channels In T Cell Physiologymentioning

confidence: 99%

“…Normally, it not only is abundantly expressed in neurons of dorsal ganglia, but also is reported in spleen and thymus in murine models [ 201 ]. Yet TRESK is strongly upregulated in several leukemic cell lines as well as in patients with T-ALL [ 197 ]. In vivo real time K + flux measurements and concurrent patch-clamp data on Jurkat cells revealed that both TRESK and K v 1.3 mediate AVD in the intrinsic apoptosis pathway, yet TRESK is transiently upregulated by apoptotic stimulus (staurosporine) and then completely inactivated in a half of hour, causing a strong membrane depolarization, whereas the K v 1.3 contribution to the K + efflux was more constant in time [ 147 ].…”

Section: Ion Channels In T Cell Physiologymentioning

confidence: 99%

“…For example, TRESK channels are abnormally expressed in some types of T leukemias [ 197 ]. As was mentioned, this channel is activated through Cn-dependent mechanism and is involved in a positive feedback regulation of the Ca 2+ entry.…”

Section: Targeting Ion Channels For the T-all Treatmentmentioning

confidence: 99%

See 2 more Smart Citations

Placing Ion Channels into a Signaling Network of T Cells: From Maturing Thymocytes to Healthy T Lymphocytes or Leukemic T Lymphoblasts

Dobrovinskaya

Delgado‐Enciso

Quintero-Castro

et al. 2015

BioMed Research International

Self Cite

View full text Add to dashboard Cite

T leukemogenesis is a multistep process, where the genetic errors during T cell maturation cause the healthy progenitor to convert into the leukemic precursor that lost its ability to differentiate but possesses high potential for proliferation, self-renewal, and migration. A new misdirecting “leukemogenic” signaling network appears, composed by three types of participants which are encoded by (1) genes implicated in determined stages of T cell development but deregulated by translocations or mutations, (2) genes which normally do not participate in T cell development but are upregulated, and (3) nondifferentially expressed genes which become highly interconnected with genes expressed differentially. It appears that each of three groups may contain genes coding ion channels. In T cells, ion channels are implicated in regulation of cell cycle progression, differentiation, activation, migration, and cell death. In the present review we are going to reveal a relationship between different genetic defects, which drive the T cell neoplasias, with calcium signaling and ion channels. We suggest that changes in regulation of various ion channels in different types of the T leukemias may provide the intracellular ion microenvironment favorable to maintain self-renewal capacity, arrest differentiation, induce proliferation, and enhance motility.

show abstract

Section: Ion Channels In T Cell Physiologymentioning

confidence: 99%

Section: Ion Channels In T Cell Physiologymentioning

confidence: 99%

See 1 more Smart Citation

Placing Ion Channels into a Signaling Network of T Cells: From Maturing Thymocytes to Healthy T Lymphocytes or Leukemic T Lymphoblasts

Dobrovinskaya

Delgado‐Enciso

Quintero-Castro

et al. 2015

BioMed Research International

Self Cite

View full text Add to dashboard Cite

show abstract

“…Later, general consensus was reached that TRESK is robustly expressed in pseudounipolar neurons of dorsal root, trigeminal and other sensory ganglia [13]–[19]. At present, these ganglia are considered as the major location of the channel, although some evidence is accumulating that it may also be important in ganglia of the autonomic nervous system [20], and in lymphoblastic cell lines [21], [22].…”

Section: Introductionmentioning

confidence: 99%

Tubulin Binds to the Cytoplasmic Loop of TRESK Background K+ Channel In Vitro

et al. 2014

View full text Add to dashboard Cite

The cytoplasmic loop between the second and third transmembrane segments is pivotal in the regulation of TRESK (TWIK-related spinal cord K+ channel, K2P18.1, KCNK18). Calcineurin binds to this region and activates the channel by dephosphorylation in response to the calcium signal. Phosphorylation-dependent anchorage of 14-3-3 adaptor protein also modulates TRESK at this location. In the present study, we identified molecular interacting partners of the intracellular loop. By an affinity chromatography approach using the cytoplasmic loop as bait, we have verified the specific association of calcineurin and 14-3-3 to the channel. In addition to these known interacting proteins, we observed substantial binding of tubulin to the intracellular loop. Successive truncation of the polypeptide and pull-down experiments from mouse brain cytosol narrowed down the region sufficient for the binding of tubulin to a 16 amino acid sequence: LVLGRLSYSIISNLDE. The first six residues of this sequence are similar to the previously reported tubulin-binding region of P2X2 purinergic receptor. The tubulin-binding site of TRESK is located close to the protein kinase A (PKA)-dependent 14-3-3-docking motif of the channel. We provide experimental evidence suggesting that 14-3-3 competes with tubulin for the binding to the cytoplasmic loop of TRESK. It is intriguing that the 16 amino acid tubulin-binding sequence includes the serines, which were previously shown to be phosphorylated by microtubule-affinity regulating kinases (MARK kinases) and contribute to channel inhibition. Although tubulin binds to TRESK in vitro, it remains to be established whether the two proteins also interact in the living cell.

show abstract

“…Acute T-ALL Jurkat cell line displays several-fold lower Kv1.3 channels density; it was reported also that these cells express small conductance KCa2.2 channels in increased numbers, compared to the levels of KCa3.1 channels in activated healthy T cells (reviewed in Dobrovinskaya et al, 2015). Data from our lab demonstrated that Jurkat cells and other T-leukemic cell lines as well as blood samples from patients with T-ALL show the expression of a tandem-pore K + (K2P) channel TRESK (Pottosin et al, 2008; Sánchez-Miguel et al, 2013). Data from other group also revealed the presence of the members of K2P channels in human T-cells (Meuth et al, 2008; Andronic et al, 2013).…”

Section: Cholinergic Signaling May Be Involved In T Leukemogenesismentioning

confidence: 99%

Cholinergic Machinery as Relevant Target in Acute Lymphoblastic T Leukemia

et al. 2016

Self Cite

View full text Add to dashboard Cite

Various types of non-neuronal cells, including tumors, are able to produce acetylcholine (ACh), which acts as an autocrine/paracrine growth factor. T lymphocytes represent a key component of the non-neuronal cholinergic system. T cells-derived ACh is involved in a stimulation of their activation and proliferation, and acts as a regulator of immune response. The aim of the present work was to summarize the data about components of cholinergic machinery in T lymphocytes, with an emphasis on the comparison of healthy and leukemic T cells. Cell lines derived from acute lymphoblastic leukemias of T lineage (T-ALL) were found to produce a considerably higher amount of ACh than healthy T lymphocytes. Additionally, ACh produced by T-ALL is not efficiently hydrolyzed, because acetylcholinesterase (AChE) activity is drastically decreased in these cells. Up-regulation of muscarinic ACh receptors was also demonstrated at expression and functional level, whereas nicotinic ACh receptors seem to play a less important role and not form functional channels in cells derived from T-ALL. We hypothesized that ACh over-produced in T-ALL may act as an autocrine growth factor and play an important role in leukemic clonal expansion through shaping of intracellular Ca2+ signals. We suggest that cholinergic machinery may be attractive targets for new drugs against T-ALL. Specifically, testing of high affinity antagonists of muscarinic ACh receptors as well as antagomiRs, which interfere with miRNAs involved in the suppression of AChE expression, may be the first choice options.

show abstract

TRESK potassium channel in human T lymphoblasts

Cited by 11 publications

References 30 publications

Placing Ion Channels into a Signaling Network of T Cells: From Maturing Thymocytes to Healthy T Lymphocytes or Leukemic T Lymphoblasts

Placing Ion Channels into a Signaling Network of T Cells: From Maturing Thymocytes to Healthy T Lymphocytes or Leukemic T Lymphoblasts

Tubulin Binds to the Cytoplasmic Loop of TRESK Background K+ Channel In Vitro

Cholinergic Machinery as Relevant Target in Acute Lymphoblastic T Leukemia

Contact Info

Product

Resources

About