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

Abstract

Non-technical summary

Mitochondrial Exchanger NCLX Plays a Major Role in the Intracellular Ca2+Signaling, Gliotransmission, and Proliferation of Astrocytes

“…Mitochondria are critically involved in Ca 2ϩ handling in astrocytes, thereby modifying astrocytic functions (Verkhratsky et al, 2012). In the present study, we addressed the specific role of NCLX in shaping astrocytic mitochondrial and cytoplasmic Ca 2ϩ signals and studied its impact on Ca 2ϩ -dependent astrocyte functions.…”

“…Recently, NCLX has been identified as the mitochondrial Na ϩ / Ca 2ϩ exchanger in several cell types (Palty et al, 2010;Kim et al, 2012). To determine whether NCLX is the mitochondrial exchanger in astrocytes, we first evaluated NCLX expression in lysates from cultures of cortical astrocytes by Western blot analysis.…”

“…NCLX activity modulates the store-operated Ca 2؉ entry in astrocytes SOCE is an important Ca 2ϩ influx pathway in nonexcitable cells such as astrocytes (Kresse et al, 2005;Pivneva et al, 2008;Verkhratsky et al, 2012). Observations in other cell types showing that the mitochondrial Ca 2ϩ shuttling machinery is essential to sustaining the activity of SOCE (Hoth et al, 1997;Malli et al, 2003;Parekh, 2008, and the reduction of the Ca 2ϩ -elevated plateau phase seen in the ATP-induced Ca 2ϩ signal in NCLXsilenced astrocytes (described above) prompted us to determine the specific influence of mitochondrial NCLX on Ca 2ϩ influx through the SOCE pathway in astrocytes.…”

“…At the neuronal synapse, for example, the mitochondrial Na ϩ /Ca 2ϩ exchanger participates in shaping Ca 2ϩ signals, thus modulating neuronal activity and synaptic plasticity (Kann and Kovács, 2007;Pizzo et al, 2012). Activity of the mitochondrial exchanger has also been documented in astrocytes, where it is closely linked to exocytotic release of glutamate and mediates a robust cytosolic and mitochondrial Na ϩ transport (Bernardinelli et al, 2006;Reyes and Parpura, 2008;Verkhratsky et al, 2012).…”

Life after the birth of the mitochondrial Na+/Ca2+ exchanger, NCLX

“…The second component is the ER, a major store of Ca 2+ that releases Ca 2+ upon activation of the inositol trisphosphate (IP3) receptor Ca 2+ channel on the ER. Interestingly, the mitochondria network is highly dynamic in lymphocytes and often moves toward the immunological synapse participating in Ca 2+ signaling in these cells [20]. In their study, Kim et al used DT40, a haploid lymphocytic cell line with a specific NCLX knockdown.…”