The calcium binding protein ALG-2 is upregulated in several types of cancerous tissues and cancer cell death may be a consequence of ALG-2 downregulation. Novel research suggests that ALG-2 is involved in membrane repair mechanisms, in line with several published studies linking ALG-2 to processes of membrane remodeling and transport, which may contribute to the fitness of cells or protect them from damage. To investigate the involvement of ALG-2 in cell recovery after membrane damage we disrupted the PDCD6 gene encoding the ALG-2 protein in DT-40 cells and exposed them to electroporation. ALG-2 knock-out cells were more sensitive to electroporation as compared to wild type cells. This phenotype could be reversed by reestablishing ALG-2 expression confirming that ALG-2 plays an important role in cell recovery after plasma membrane damage. We found that overexpression of wild type ALG-2 but not a mutated form unable to bind Ca²⁺ partially protected HeLa cells from digitonin-induced cell death. Further, we were able to inhibit the cell protective function of ALG-2 after digitonin treatment by adding a peptide with the ALG-2 binding sequence of ALIX, which has been proposed to serve as the ALG-2 downstream target in a number of processes including cell membrane repair. Our results suggest that ALG-2 may serve as a novel therapeutic target in combination with membrane damaging interventions.

钙结合蛋白ALG-2在几种类型的癌组织中上调，癌细胞死亡可能是ALG-2下调的结果。新颖的研究表明，ALG-2参与了膜修复机制，这与多项将ALG-2与膜重塑和运输过程联系在一起的研究一致，这可能有助于细胞的适应性或保护其免受损伤。为了研究膜损伤后ALG-2与细胞恢复的关系，我们破坏了PDCD6编码DT-40细胞中ALG-2蛋白的基因，并将其暴露于电穿孔中。与野生型细胞相比，ALG-2敲除细胞对电穿孔更为敏感。该表型可以通过重新建立ALG-2表达来逆转，从而证实ALG-2在质膜受损后在细胞恢复中起着重要作用。我们发现野生型ALG-2的过表达，但不是无法结合Ca ²⁺的突变形式部分保护HeLa细胞免受洋地黄菌素诱导的细胞死亡。此外，我们可以通过添加具有ALIX的ALG-2结合序列的肽来抑制洋地黄素处理后ALG-2的细胞保护功能，该肽已被提议在许多过程中用作ALG-2下游靶标包括细胞膜修复。我们的结果表明，ALG-2可以与膜破坏性干预措施结合起来用作新型治疗靶标。