Requirement of Voltage-Gated Calcium Channel b₄ Subunit For T Lymphocyte Functions (1)

Speaker:                   吳 怡 靜                        Time: 14:00-15:00 Mar 2, 2005

Commentator:      謝 奇 璋  老師               Place: Room 601

Abstract:

On T lymphocytes, ligation of the antigen receptor induces a biphasic calcium response, which leads to activation of calcineurin and NFAT that regulates T cell functions. In the initial phase, Ca²⁺released from intracellular stores increase the intracellular Ca²⁺ concentration, followed by a lower, but prolonged elevation that is dependent on extracellular Ca²⁺(2). Several different intracellular and plasma membrane Ca²⁺ channels are involved in this response. Their functions in T cell regulation remain unclear. Voltage-gated calcium channels (Ca_v), belonging to the plasma membrane Ca²⁺ channels, are essential for calcineurin activation and NFAT function in neurons (3). Ca_v b₄ is a major subunit associated with Ca_v1 channels. Mutation of Ca_v b₄ causes defective cell-mediated immune responses in mice. In this study, the authors investigated how Ca²⁺ signals are regulated after TCR ligation. They found that b₄ subunit is expressed in naïve T cells, and up-regulated after TCR engagement. Ca_v b₄-mutant T cells fail to acquire normal functions and display impairment in the calcium response, activation of NFAT, and cytokine production. Furthermore, Ca_v1 channel expressed in T cells still retain their ability to respond to voltage. Although only a small depolarization was detected upon TCR stimulation, it is sufficient to induce further responses. This depolarization might play a role in regulating Ca_v1 channels, or Ca_v1 channels could be regulated by another voltage-independent manner. Overall, this study provides an answer to a long-standing question about the molecular nature of calcium channels present in T cells.

References:

1.     Badou A, et al. 2005. Requirement of voltage-gated calcium channel b₄ subunit for T lymphocyte functions. Science 307:117.

2.     Grafton G, et al. 2001. Calcium channels in lymphocytes. Immunology 104:119.

3.     Winslow MM, et al. 2005. Decoding calcium signaling. Science 307:56.