Cell Biology and Neurobiology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
Cell Biology and Neurobiology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892
Proc Natl Acad Sci U S A. 2017 Apr 4;114(14):E2955-E2964. doi: 10.1073/pnas.1616363114. Epub 2017 Mar 20.
The ability of lysosomes to move within the cytoplasm is important for many cellular functions. This ability is particularly critical in neurons, which comprise vast, highly differentiated domains such as the axon and dendrites. The mechanisms that control lysosome movement in these domains, however, remain poorly understood. Here we show that an ensemble of BORC, Arl8, SKIP, and kinesin-1, previously shown to mediate centrifugal transport of lysosomes in nonneuronal cells, specifically drives lysosome transport into the axon, and not the dendrites, in cultured rat hippocampal neurons. This transport is essential for maintenance of axonal growth-cone dynamics and autophagosome turnover. Our findings illustrate how a general mechanism for lysosome dispersal in nonneuronal cells is adapted to drive polarized transport in neurons, and emphasize the importance of this mechanism for critical axonal processes.
溶酶体在细胞质内移动的能力对于许多细胞功能很重要。这种能力在神经元中尤为关键,神经元包含了巨大的、高度分化的区域,如轴突和树突。然而,控制这些区域中溶酶体运动的机制仍知之甚少。在这里,我们表明,先前在非神经元细胞中显示介导溶酶体向心运输的 BORC、Arl8、SKIP 和驱动蛋白-1 复合物,特异性地将溶酶体运输到培养的大鼠海马神经元的轴突中,而不是树突中。这种运输对于维持轴突生长锥动力学和自噬体周转至关重要。我们的发现说明了非神经元细胞中溶酶体弥散的一般机制如何适应于驱动神经元中的极化运输,并强调了该机制对于关键的轴突过程的重要性。