細胞體積調控是一種控制電解質與水進出細胞膜的動態過程。大多數的哺乳類動物細胞透過溶質與水分排出細胞來抵禦外界低滲透濃度的壓力，這樣的過程我們稱之為細胞調控體積下降regulatory volume decrease (RVD)。 我們發現在細胞中主要負責抵抗細胞凋亡的蛋白質Bcl-2同時具有一種嶄新的功能，那就是在細胞調控體積下降與離子流動。Bcl-2蛋白質家族能夠插入脂質雙層膜並作為離子通道；Bcl-2本身也可以因為藉由與FAK/Paxillin結合而具有影響Focal adhesions區的潛力。我們提出Bcl-2可以扮演調節細胞體積與細胞黏附的作用，因為該蛋白質在立體結構上，5與6螺旋構造正好是其形成孔洞的位置，而將5螺旋中的WGR 144-146胺基酸位點作突變，會使Bcl-2失去其原有的抵抗細胞凋亡功能。我們在MDCK細胞中建立了WGR144-146突變的細胞株，依Bcl-2蛋白表現量不同分別稱作mI-2.4, mI-2.7。我們在低張溶液下比較了控制株C1、野生型B6與突變型mI-2.4, mI-2.7細胞的體積調控能力。我們發現突變株不只是失去了原有野生型具備的增強體積調節能力，反而更加速破壞了細胞所具有調控體積下降的能力。而在細胞貼附的實驗中，我們發現在不同的細胞外基質中，突變株都很明顯的使細胞貼附與細胞移行的能力下降了。這些結果證明了Bcl-2的WRG 144-146位點對於細胞體積調節、細胞貼附與細胞移行的重要性。

Cell volume regulations are dynamic processes which control electrolytes and water movement across cell membrane. Most mammalian cells defend themselves against hypotonic stress by losing solutes together with osmotically obligated water, a process termed regulatory volume decrease (RVD). We have found that the key regulatory anti apoptotic protein Bcl-2 has a novel function on RVD and ion flux. Bcl-2 family proteins can insert in lipid bilayer and act as ion channels. Bcl-2 can also form a complex with paxillin/FAK which potentially influences cell adhesion signaling. Thus, we propose that Bcl-2 may function as a regulator of volume regulation and cell adhesion. Because 5-6 helices construct a critical region in pore forming of Bcl-2, mutation of WGR 144-146 motif at 5 helix results in disruption of Bcl-2 anti-apoptosis function. Two stable transfectants harboring WGR 144-146 motif of BH1 domain mutant Bcl-2 gene were established in MDCK cells, namely mI-2.4, mI-2.7. We compared the volume change of the plasmid control (C1), Bcl-2 wild-type (B6), and Bcl-2 mutant cells following superfusion with hypotonic solutions. We found that mutation of Bcl-2 not only abolished Bcl-2-induced increased in RVD, but also disrupted Bcl-2-accelerated RVD. In cell adhesion assay, Bcl-2 mutant cells showed markedly reduced adhesion and migration function on different extracellular matrix. These results indicate that WGR 144-146 motif is important for the novel function of Bcl-2 in cell volume regulation as well as cell adhesion and migration.

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