National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892, USA.
J Neurosci. 2012 Mar 7;32(10):3398-404. doi: 10.1523/JNEUROSCI.5943-11.2012.
Endocytosis overshoot, which retrieves more membrane than vesicles just being exocytosed, occurs at nerve terminals and non-neuronal secretory cells. The mechanism that retrieves the overshoot membrane pool and the role of this pool remain largely unknown. We addressed this issue at the rat calyx of Held nerve terminal with capacitance measurements. We found that every calyx contained an overshoot pool ∼1.8 times the readily releasable pool. Retrieval of this pool required large calcium influx, and was inhibited by blockers of calcium/calmodulin-activated calcineurin and dynamin, suggesting the involvement of calcineurin and dynamin in endocytosis overshoot. Depletion of the overshoot pool slowed down compensatory endocytosis, whereas recovery of the overshoot pool via exocytosis that deposited stranded vesicles to the plasma membrane led to recovery of compensatory endocytosis, suggesting that the overshoot pool enhances endocytosis efficiency. These results suggest that the overshoot pool exists at every nerve terminal, is of limited size arising from vesicles stranded at the plasma membrane, is retrieved via calcium/calmodulin/calcineurin and dynamin signaling pathway, and can enhance endocytosis efficiency. Potential mechanisms for how the endocytosis overshoot pool enhances endocytosis efficiency are discussed.
内吞作用过冲是指在神经末梢和非神经元分泌细胞中，内吞回收的膜量超过正在胞吐的囊泡。这种过冲膜池的回收机制及其作用在很大程度上仍然未知。我们使用电容测量法研究了大鼠蜗状神经末梢的钙调神经磷酸酶和动力蛋白在这一过程中的作用。结果发现，每个蜗状体内都有一个过冲池，其大小约为易释放池的 1.8 倍。该池的回收需要大量钙离子内流，且被钙/钙调蛋白激活的钙调神经磷酸酶和动力蛋白抑制剂所抑制，提示钙调神经磷酸酶和动力蛋白参与了内吞作用过冲。过冲池的耗竭会减缓补偿性内吞作用，而过冲池通过将滞留于质膜的丝状囊泡胞吐至质膜来恢复，这会导致补偿性内吞作用的恢复，表明过冲池可增强内吞作用效率。这些结果表明，过冲池存在于每个神经末梢，其大小有限，来源于质膜上滞留的囊泡，通过钙/钙调蛋白/钙调神经磷酸酶和动力蛋白信号通路进行回收，并可增强内吞作用效率。文中讨论了过冲池如何增强内吞作用效率的潜在机制。
