Changes in lysosome shape and distribution correlated with changes in cytoplasmic pH.
Changes in lysosome shape and distribution correlated with changes in cytoplasmic pH.
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溶酶体形状和分布的变化与细胞质pH的变化相关。
DOI：
10.1083/jcb.108.3.855
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发表时间：
1989-03
期刊：
影响因子：
--
通讯作者：
Heuser J
中科院分区：
文献类型：
--
作者：
Heuser J
当通过实验改变细胞质 pH 值时，通过摄取细胞外辣根过氧化物酶标记的溶酶体在形状和细胞分布上表现出显着的变化。通常，巨噬细胞和成纤维细胞中的溶酶体聚集在细胞中心周围。然而，当通过施加乙酸盐或通过各种其他方式将细胞质 pH 值降低至大约 pH 6.5 时，溶酶体会迅速向外移动并在细胞的最边缘聚集成紧密的簇，特别是在酸化前活跃的波动但变得静止的区域。这种运动遵循这些细胞中微管的分布，如果在酸化之前用诺考达唑解聚微管，则不会发生这种运动。随后去除乙酸盐或其他酸化刺激物会导致皱褶活动迅速恢复，并使溶酶体返回到细胞中心的紧密簇中。这与细胞质的碱化反弹相关。相应地，直接应用弱碱也会导致溶酶体过度波动和异常完全撤回细胞中心。因此，溶酶体似乎受到顺行（驱动蛋白）类型和逆行（动力蛋白）类型的基于微管的马达的作用，或者它们具有通过细胞质pH的变化而逆转的双向马达。在酸化诱导的向外运动过程中，溶酶体也似乎比正常情况更小，并且更多地呈囊泡状，而在向内运动过程中，它们似乎比正常情况更加汇合和拉长，通常变得比佛波醇处理的巨噬细胞更加管状（Phaire-Washington, L., S. C. Silverstein, and E. Wang. 1980. J. Cell Biol. 86：641-655）。这些大小和形状的变化表明细胞质 pH 值也会影响溶酶体的融合/裂变特性。结合 pH 对其运动的影响，从酸化恢复过程中的最终结果是溶酶体沿着微管拉伸成管状形式。
Lysosomes labeled by uptake of extracellular horseradish peroxidase display remarkable changes in shape and cellular distribution when cytoplasmic pH is experimentally altered. Normally, lysosomes in macrophages and fibroblasts cluster around the cell center. However, when the cytoplasmic pH is lowered to approximately pH 6.5 by applying acetate or by various other means, lysosomes promptly move outward and accumulate in tight clusters at the very edge of the cell, particularly in regions that are actively ruffling before acidification but become quiescent. This movement follows the distribution of microtubules in these cells, and does not occur if microtubules are depolymerized with nocodazole before acidification. Subsequent removal of acetate or the other stimuli to acidification results in prompt resumption of ruffling activity and return of lysosomes into a tight cluster at the cell center. This is correlated with a rebound alkalinization of the cytoplasm. Correspondingly, direct application of weak bases also causes hyperruffling and unusually complete withdrawal of lysosomes to the cell center. Thus, lysosomes appear to be acted upon by microtubule- based motors of both the anterograde (kinesin) type as well as the retrograde (dynein) type, or else they possess bidirectional motors that are reversed by changes in cytoplasmic pH. During the outward movements induced by acidification, lysosomes also appear to be smaller and more predominantly vesicular than normal, while during inward movements they appear to be more confluent and elongated than normal, often becoming even more tubular than in phorbol-treated macrophages (Phaire-Washington, L., S. C. Silverstein, and E. Wang. 1980. J. Cell Biol. 86:641-655). These size and shape changes suggest that cytoplasmic pH also affects the fusion/fission properties of lysosomes. Combined with pH effects on their movement, the net result during recovery from acidification is a stretching of lysosomes into tubular forms along microtubules.