Store-operated Calcium Channels and Severe Combined Immune Deficiency Syndrome

鈣離子通道調控與嚴重合併性免疫不全症候群

張偉斌(Wei-Pin Chang) ； 黃育文(Yu-Wen Huang) ； 吳振龍(Chen-Long Wu) ； 劉德明(Der-Ming Liu)

《北市醫學雜誌》 4卷1期 (2007/01) Pp. 13-18

https://doi.org/10.6200/TCMJ.2007.4.1.02

摘要

在哺乳動物中，細胞內鈣離子濃度變化扮演著相當重要的生理角色。舉例來說，細胞內鈣離子經常被認為是一種給予生命的信號，因為它參與著調控精子的活動能力，也是維持生命所必須。不同的頻率的細胞內鈣離子濃度波動可以調節完全不同的生理功能，例如細胞胞吐作用、基因轉錄、與細胞生長…等等。細胞內鈣離子除了扮演著給予生命的信號之外，也可以透過啟動細胞凋亡機制或細胞壞死機制來執行讓細胞死亡的角色。在非興奮細胞如：T細胞或肥大細胞，鈣離子主要是透過鈣池調控鈣離子通道(store-operated Ca(上標 2+) channels)進入細胞內。當細胞外在因子刺激時，可以活化生成InsP3，促使內質網的鈣離子外流，進而降低內質網中鈣離子濃度，啟動細胞膜上的鈣池調控鈣離子通道；實驗上，也可以給予細胞thapsigarin或EGTA、BAPTA…等等，來開啟離子通道。儘管這個領域受到愈來愈多的重視，然而，鈣池調控鈣離子通道所能影響的細胞生理意義或其調控機制，至今所知仍然非常有限。Orai1是第一個被發現與鈣池調控鈣離子通道的開啟有關的基因。在嚴重型合併性免疫不全家族的T細胞中，可以發現Orai1基因發生突變，而這個不但影響鈣池調控鈣離子通道的開啟，也會抑制免疫基因的活化。這些病人通常在幼年就因為各種感染而死亡。

關鍵字

鈣池調控鈣離子通道 ； 嚴重型合併性免疫不全

並列摘要

An increase of cytoplasmic Ca(superscript 2+) concentration is used as a key signaling messenger in several mammalian cells. Ca(superscript 2+) regulates a broad spectrum of physiological processes. Intracellular Ca(superscript 2+) is often considered a ”life-giving” signal because it is essential for sperm motility and is also necessary for sustaining the life. Distinct temporal patterns of cytoplasmic Ca(superscript 2+) increases drive different processes such as exocytosis, gene transcription, and cell growth. In additional to have given life, Ca(superscript 2+) also can take it away. This opposite side of the Ca(superscript 2+) signal can be executed through apoptosis or necrosis. In non-excitable cells such as T cells and mast cells, one major route for Ca(superscript 2+) influx is through store-operated Ca(superscript 2+) channels in the plasma membrane. Store-operated Ca(superscript 2+) influx is controlled by the Ca(superscript 2+) concentration within the intracellular stores. When the Ca(superscript 2+) concentration falls, a signal somehow is sent from the stores to open the Ca(superscript 2+) channels. Experimentally, stores can be emptied by increasing of InsP3 molecule in the cytosol, dialyzing the cytoplasm to high concentrations of Ca(superscript 2+) chelators such as EGTA or BAPTA, or treating with the endoplasmic/sarcoplasmic reticulum Ca(superscript 2+) ATPase (SERCA) inhibitors like thapsigargin and cyclopiazonic acid. Despite considerable attention, neither the gating mechanism nor the physiological function of these channels has been resolved. Orai1 was first identified form genetic analysis to find the mutations contributing to severe combined immune deficiency by interfering store-operated calcium channels. The T cells from these patients lack store-operated calcium channels which results in the inactivation of immune genes, and these patients usually die due to the infection in infancy.

並列關鍵字

store-operated calcium channels ； severe combined immune deficiency SCID