Autophagosomes initiate distally and mature during transport toward the cell soma in primary neurons.
Autophagosomes initiate distally and mature during transport toward the cell soma in primary neurons.
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DOI：
10.1083/jcb.201106120
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发表时间：
2012-02-20
期刊：
影响因子：
--
通讯作者：
Holzbaur EL
中科院分区：
文献类型：
--
作者：
Maday S;Wallace KE;Holzbaur EL
在原代神经元中，自噬体的生物发生和成熟是一个组成性过程，在轴突上受到时空调节。
自噬是神经元中一种重要的细胞降解途径；自噬缺陷足以诱导神经退行性变。在本文中，我们研究了原代背根神经节神经元中的自噬体动力学。自噬体的生物发生在神经突末端以一种组成性过程在远端发生。自噬体最初双向移动，然后转变为由动力蛋白驱动的朝向细胞体的单向、持续性移动。自噬体与顺向和逆向运动蛋白共同纯化，这表明结合的驱动蛋白运动活性被有效下调，从而产生由动力蛋白驱动的强大逆向运动性。细胞器和可溶性货物都被内化到自噬体中，包括线粒体和泛素。随着自噬体从远端向近端移动，它们经历成熟过程并变得越来越酸化，这与自溶酶体区室的形成一致，该自溶酶体区室可能更有效地降解货物。这种成熟过程伴随着向溶酶体所特有的双向运动性的转变。总之，原代神经元中自噬体的生物发生和成熟是一个在轴突上受到时空调节的组成性过程。
Autophagosome biogenesis and maturation in primary neurons is a constitutive process that is spatially and temporally regulated along the axon. Autophagy is an essential cellular degradation pathway in neurons; defects in autophagy are sufficient to induce neurodegeneration. In this paper, we investigate autophagosome dynamics in primary dorsal root ganglion neurons. Autophagosome biogenesis occurs distally in a constitutive process at the neurite tip. Autophagosomes initially move bidirectionally and then switch to unidirectional, processive movement toward the cell soma driven by dynein. Autophagosomes copurify with anterograde and retrograde motors, suggesting that the activity of bound kinesin motors is effectively down-regulated to yield robust retrograde motility driven by dynein. Both organelle and soluble cargoes are internalized into autophagosomes, including mitochondria and ubiquitin. As autophagosomes move distally to proximally, they undergo maturation and become increasingly acidified, consistent with the formation of an autolysosomal compartment that may more efficiently degrade cargo. This maturation is accompanied by a switch to bidirectional motility characteristic of lysosomes. Together, autophagosome biogenesis and maturation in primary neurons is a constitutive process that is spatially and temporally regulated along the axon.
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DOI：
10.1523/jneurosci.6412-10.2011
发表时间：
2011-05-25
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Lee S;Sato Y;Nixon RA
通讯作者：
Nixon RA
影响因子：
7.8
作者：
Quintyne, N J;Gill, S R;Eckley, D M;Crego, C L;Compton, D A;Schroer, T A
通讯作者：
Schroer, T A
影响因子：
3.3
作者：
van der Vaart A;Griffith J;Reggiori F
通讯作者：
Reggiori F
DOI：
10.1083/jcb.200904075
发表时间：
2010-01-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Yen WL;Shintani T;Nair U;Cao Y;Richardson BC;Li Z;Hughson FM;Baba M;Klionsky DJ
通讯作者：
Klionsky DJ
影响因子：
3.3
作者：
Mizushima, N;Yamamoto, A;Ohsumi, Y
通讯作者：
Ohsumi, Y