Let's play a game of chutes and ladders: Lysosome fusion with the epithelial plasma membrane.
Let's play a game of chutes and ladders: Lysosome fusion with the epithelial plasma membrane.
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DOI：
10.4161/cib.24474
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发表时间：
2013-07-01
影响因子：
--
通讯作者：
Lakkaraju A
中科院分区：
文献类型：
--
作者：
Toops KA;Lakkaraju A
在非极化细胞中，钙诱导的“常规”溶酶体胞外分泌在暴露于形成孔的毒素后的膜修复和细胞碎片的清除等多种过程中都很重要。撕裂膜的重新密封对于直接与病原体和毒素相互作用的屏障上皮尤其重要，这可能导致膜微破坏和病变。然而，溶酶体是否参与极化上皮的膜修复一直是一个悬而未决的问题。我们最近报道了极化的Madin-Darby犬肾（MDCK）细胞，钙的局部内流诱导溶酶体与基底外膜融合。胞吐作用的空间分离取决于完整的肌动蛋白细胞骨架、膜胆固醇和融合机制（如t-SNARE syntaxin 4）的有限分布。我们的数据表明，syntaxin 4的极性（由网格蛋白接头蛋白AP-1调节）决定了溶酶体是降落伞降落到基侧膜还是采取阶梯上升到顶膜。在这里，我们推测其他机制（如溶酶体钙传感器synaptotagmin VII和v-SNARE VAMP7）可能参与溶酶体与上皮膜的极化融合。我们还讨论了溶酶体胞吐在维持视网膜色素上皮膜完整性方面的潜在重要性，视网膜色素上皮是致盲性疾病（如年龄相关性黄斑变性）的主要组织。
In non-polarized cells, calcium-induced exocytosis of “conventional” lysosomes is important in diverse processes like membrane repair after exposure to pore-forming toxins and clearance of cellular debris. Resealing of torn membranes is especially critical for barrier epithelia that directly interact with pathogens and toxins, which can result in membrane microdisruptions and lesions. However, whether lysosomes participate in membrane repair in polarized epithelia has been an open question. We recently reported that in polarized Madin-Darby canine kidney (MDCK) cells, localized influx of calcium induces lysosomes to fuse with the basolateral membrane. This spatial segregation of exocytosis depends on an intact actin cytoskeleton, membrane cholesterol and restricted distribution of fusion machinery such as the t-SNARE syntaxin 4. Our data show that the polarity of syntaxin 4 (which is regulated by the clathrin adaptor protein AP-1) dictates whether lysosomes parachute down to the basolateral membrane or take a ladder up to the apical membrane. Here, we speculate about additional machinery (such as the lysosomal calcium sensor synaptotagmin VII and the v-SNARE VAMP7) that could be involved in polarized fusion of lysosomes with the epithelial membrane. We also discuss the potential importance of lysosome exocytosis in maintaining membrane integrity in the retinal pigment epithelium, the primary tissue affected in blinding diseases such as age-related macular degeneration.