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Selective calcium blockade

Bcl-2 blocks deadly, persistent Ca²⁺ increases but allows signaling Ca²⁺ oscillations to proceed, according to Zhong et al. (page 127). As a result, this antiapoptotic protein can save T cells from death without interfering with other Ca²⁺-regulated cell functions.

Calcium has a hand in many physiological processes, including the proliferation of activated T cells. So the authors were a bit perplexed when they previously discovered that Bcl-2 inhibited IP₃ receptors (IP₃Rs), which release Ca²⁺ from the ER. But they now find that only persistent Ca²⁺ increases are affected by Bcl-2.

These persistent increases, or "transients," result from high concentrations of antibodies, which activate T cell receptor (TCR) signaling and induce apoptosis. Although low antibody concentrations also activate TCRs, they lead to lasting Ca²⁺ oscillations that favor cell survival. These oscillations were not blocked by Bcl-2. RNAi-mediated loss of IP₃Rs also did not prevent Ca²⁺ oscillations. Perhaps, in T cells, oscillations are IP₃R-independent or require only very few of these receptors.

Bcl-2 expression in T cells is temporarily down-regulated in the thymic cortex, where positive and negative selection occur. Its loss thus allows strong TCR reactions—as caused by self-antigens—to kill the T cell. In the periphery, however, the presence of Bcl-2 might protect mature T cells that encounter a strong antigen.

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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Related Article

Bcl-2 differentially regulates Ca²⁺ signals according to the strength of T cell receptor activation

Fei Zhong, Michael C. Davis, Karen S. McColl, and Clark W. Distelhorst
J. Cell Biol. 2006 172: 127-137. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 340K) Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Related Collections Related Article Social Bookmarking                            What's this?