geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Pivotal role of mitochondrial Na⁺₋Ca²⁺ exchange in antigen receptor mediated Ca²⁺ signalling in DT40 and A20 B lymphocytes


, : Pivotal role of mitochondrial Na⁺₋Ca²⁺ exchange in antigen receptor mediated Ca²⁺ signalling in DT40 and A20 B lymphocytes. Journal of Physiology 590(3): 459-474

Cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) increases upon activation of antigen-receptor in lymphocytes. Mitochondria have been suggested to regulate the [Ca(2+)](i) response, but the molecular mechanisms and the roles are poorly understood. To clarify them, we carried out a combination study of mathematical simulations and knockout or knockdown of NCLX, a gene candidate for the mitochondrial Na(+)-Ca(2+) exchanger (NCX(mit)), in B lymphocytes. A mathematical model of Ca(2+) dynamics in B lymphocytes demonstrated that NCX(mit) inhibition reduces basal Ca(2+) content of endoplasmic reticulum (ER) and suppresses B-cell antigen receptor (BCR)-mediated [Ca(2+)](i) rise. The predictions were validated in DT40 B lymphocytes of heterozygous NCLX knockout (NCLX(+/-)). In NCLX(+/-) cells, mitochondrial Ca(2+) efflux via NCX(mit) was strongly decelerated, suggesting NCLX is a gene responsible for NCX(mit) in B lymphocytes. Consistent with the predictions, ER Ca(2+) content declined and [Ca(2+)](i) hardly rose upon BCR activation in NCLX(+/-) cells. ER Ca(2+) uptake was reduced to ∼58% of the wild-type (WT), while it was comparable to WT when mitochondrial respiration was disturbed. Essentially the same results were obtained by a pharmacological inhibition or knockdown of NCLX by siRNA in A20 B lymphocytes. Unexpectedly, ER Ca(2+) leak was augmented and co-localization of mitochondria with ER was lower in NCLX(+/-) and NCLX silenced cells. Taken together, we concluded that NCLX is a key Ca(2+) provider to ER, and that NCLX-mediated Ca(2+) recycling between mitochondria and ER is pivotal in B cell responses to antigen.

US$19.90

PMID: 22155933

DOI: 10.1113/jphysiol.2011.222927


Other references

Nazarenko, S.A.; Ostroverkhova, N.V., 1991: Localization of the gene controlling the human cell cycle in region q21 of chromosome 10 by in situ hybridization. Genetika 27(1): 165-167

Rietzel, E.; Schardt, D.; Haberer, T., 2007: Range accuracy in carbon ion treatment planning based on CT-calibration with real tissue samples. The precision in carbon ion radiotherapy depends on the calibration of Hounsfield units (HU) as measured with computed tomography (CT) to water equivalence. This calibration can cause relevant differences between treatment planning and treatment d...

Csoknya, M.; Halasy, K., 1974: Date on the distribution of mayfly larvae (Ephemeroptera). Tiscia, 9: 71-75

Defanti, C.A.; Brambilla, A.; Erli, L.C.; Tredici, G., 1984: Acute polyradiculoneuritis (Guillain-Barré) associated with the syndrome of inappropriate ADH secretion (Schwartz-Bartter): initial symptom of pulmonary neoplasia. Rivista di Neurobiologia 30(2-3): 303-308

Bonen, A.; Shaw, S.M., 1995: Recreational exercise participation and aerobic fitness in men and women: analysis of data from a national survey. We compared the relationship between predicted ovrhdot VO-2 max (ml kg-1min-1) and recreational exercise patterns, using secondary data analysis of a comprehensive national survey (18,293 subjects aged 15-69 years). Exercise participation and pred...

Ali, S.A.; Steinkasserer, A., 1995: PCR-ligation-PCR mutagenesis: a protocol for creating gene fusions and mutations. Biotechniques 18(5): 746-750

Schöffl, F.; Key, J.L., 1983: Identification of a multigene family for small heat shock proteins in soybean and physical characterization of one individual gene coding region. Confirmation, based on both the complexity and similarity of Southern blot hybridization patterns of genomic DNA digests with heat shock protein class I cDNA probes, is presented that a new class of highly abundant RNAs, which encode a group of he...

Patel, K., 2012: Profit is not a dirty word. Bmj 345: E5376-E5376

Chumakov V.I.; Kolosov V.V., 1981: Kinetics of leukocyte content in the peripheral blood and their adhesion to lung capillary endothelium in experimental vagus neuritis. Chronic experiments on rats with dextral vagus neuritis revealed that reactive leukocytosis is wave-like in character. Variations in leukocytosis were inversely proportional to adhesiveness of the lung capillary endothelium with respect to leukocy...

Guo, B.; Liang, Y.; Zhu, Y., 2008: Does salicylic acid regulate antioxidant defense system, cell death, cadmium uptake and partitioning to acquire cadmium tolerance in rice?. Salicylic acid (SA) may accelerate the cell death of cadmium-stressed roots to avoid cadmium (Cd) uptake by plants or may play positive roles in protecting the stressed roots from Cd-induced damage. To test these hypotheses, we performed a series...