Wu Xin-Sheng, Zhang Zhen, Zhao Wei-Dong, Wang Dongsheng, Luo Fujun, Wu Ling-Gang
National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA.
National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA.
Cell Rep. 2014 May 22;7(4):982-8. doi: 10.1016/j.celrep.2014.04.020. Epub 2014 May 15.
Calcium influx triggers and accelerates endocytosis in nerve terminals and nonneuronal secretory cells. Whether calcium/calmodulin-activated calcineurin, which dephosphorylates endocytic proteins, mediates this process is highly controversial for different cell types, developmental stages, and endocytic forms. Using three preparations that previously produced discrepant results (i.e., large calyx-type synapses, conventional cerebellar synapses, and neuroendocrine chromaffin cells containing large dense-core vesicles), we found that calcineurin gene knockout consistently slowed down endocytosis, regardless of cell type, developmental stage, or endocytic form (rapid or slow). In contrast, calcineurin and calmodulin blockers slowed down endocytosis at a relatively small calcium influx, but did not inhibit endocytosis at a large calcium influx, resulting in false-negative results. These results suggest that calcineurin is universally involved in endocytosis. They may also help explain the discrepancies among previous pharmacological studies. We therefore suggest that calcineurin should be included as a key player in mediating calcium-triggered and -accelerated vesicle endocytosis.
钙离子内流触发并加速神经末梢和非神经元分泌细胞的内吞作用。钙/钙调蛋白激活的钙调神经磷酸酶可使内吞蛋白去磷酸化，对于不同细胞类型、发育阶段和内吞形式而言，它是否介导这一过程存在很大争议。我们使用了三种先前产生不一致结果的制剂（即大花萼型突触、传统小脑突触以及含有大致密核心囊泡的神经内分泌嗜铬细胞），发现无论细胞类型、发育阶段或内吞形式（快速或缓慢）如何，钙调神经磷酸酶基因敲除均会持续减缓内吞作用。相比之下，钙调神经磷酸酶和钙调蛋白阻滞剂在相对较小的钙离子内流时会减缓内吞作用，但在大量钙离子内流时并不抑制内吞作用，从而导致假阴性结果。这些结果表明钙调神经磷酸酶普遍参与内吞作用。它们或许也有助于解释先前药理学研究之间的差异。因此，我们建议将钙调神经磷酸酶视为介导钙离子触发和加速的囊泡内吞作用的关键参与者。
