Autophagosome biogenesis in primary neurons follows an ordered and spatially regulated pathway.
Autophagosome biogenesis in primary neurons follows an ordered and spatially regulated pathway.
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DOI：
10.1016/j.devcel.2014.06.001
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发表时间：
2014-07-14
影响因子：
11.8
通讯作者：
Holzbaur, Erika L. F.
中科院分区：
文献类型：
--
作者：
Maday, Sandra;Holzbaur, Erika L. F.
自噬是神经元中一条重要的降解途径，但在高度极化的细胞中，自噬的机制尚不清楚。在这里，我们使用双色活细胞成像来研究原代DRG和海马培养物中组成性自噬体生物合成的神经元特异性机制。在基础条件下，轴突尖端不断产生自噬体。有一个有序的组装蛋白质招募与定型动力学发展中的自噬体。血浆或神经元衍生的膜不被纳入远端轴突的新生自噬体中。相反，自噬体产生于内质网的DFCP 1阳性亚结构域，不同于ER出口位点。生物发生事件在远端高度富集;自噬体很少在树突、细胞索马或轴突中形成，这与初级神经元中组成性自噬的高度区室化途径一致。这种远端生物发生可能有助于通过缓慢的轴突运输到达轴突尖端的受损线粒体和长寿细胞质蛋白的降解。
Autophagy is an essential degradative pathway in neurons, yetlittle is known about the mechanisms driving this process in highly polarized cells. Here, we use dual-color live-cell imaging to investigate the neuron-specific mechanisms of constitutiveautophagosome biogenesis in primary DRG and hippocampal cultures. Under basal conditions autophagosomes are continuously generated in the axon tip. There is an ordered assembly of proteins recruited with stereotypical kinetics onto the developing autophagosome. Plasma- or mitochondrial-derived membraneswere not incorporated into nascent autophagosomes in the distal axon. Rather, autophagosomes are generated at DFCP1-positive subdomains of the endoplasmic reticulum, distinct from ER exit sites. Biogenesis events arehighly enriched distally; autophagosomes form infrequently in dendrites, the cell soma or mid-axon, consistent with a highly compartmentalized pathway for constitutive autophagy in primary neurons. This distal biogenesis may facilitate the degradation of damaged mitochondria and long-lived cytoplasmic proteins that reach the axon tip via slow axonal transport.
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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
DOI：
10.1083/jcb.152.4.657
发表时间：
2001-02-19
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mizushima N;Yamamoto A;Hatano M;Kobayashi Y;Kabeya Y;Suzuki K;Tokuhisa T;Ohsumi Y;Yoshimori T
通讯作者：
Yoshimori T
酵母突变体在细胞质中的分离和表征与液泡蛋白靶向途径的分离。
影响因子：
7.8
作者：
HARDING, TM;MORANO, KA;SCOTT, SV;KLIONSKY, DJ
通讯作者：
KLIONSKY, DJ
DOI：
10.1083/jcb.201106120
发表时间：
2012-02-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Maday S;Wallace KE;Holzbaur EL
通讯作者：
Holzbaur EL
影响因子：
14.8
作者：
Kaech, Stefanie;Banker, Gary
通讯作者：
Banker, Gary