Reticulon-3 Promotes Endosome Maturation at ER Membrane Contact Sites.

Reticulon-3 Promotes Endosome Maturation at ER Membrane Contact Sites.
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DOI:
10.1016/j.devcel.2020.12.014
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发表时间:
2021-01-11
期刊:
影响因子:
11.8
通讯作者:
Voeltz GK
Voeltz GK
中科院分区:
生物学1区
文献类型:
--
作者:
Wu H;Voeltz GK

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内质网小管形成并维持与内体的膜接触位点(MCS)。这些ER-内体MCS如何以及为什么作为内体运输和成熟而持续存在还知之甚少。我们发现Reticulon蛋白家族的成员Reticulon-3L(Rtn 3L)在内体成熟时浓缩ER-内体MCS。我们发现,这种定位是由于长期分歧的N-末端胞质结构域的Rtn 3L。我们发现Rtn 3L被内体蛋白Rab 9a募集到ER-内体MCSs,这标志着早期和晚期内体之间的过渡阶段。Rab 9a利用FSV区域通过其六个LC 3相互作用区域基序募集Rtn 3L。与我们的定位结果一致,RTN 3从细胞中的耗尽或缺失导致内体成熟和货物分选缺陷,类似于RAB 9A耗尽。总之,我们的数据确定了一个管状ER蛋白,促进内体成熟的ER MCSs。Wu和Voeltz表征了一种管状内质网蛋白Reticulon-3L,其被Rab 9a募集到核内体以协调核内体成熟。
ER tubules form and maintain membrane contact sites (MCSs) with endosomes. How and why these ER-endosome MCSs persist as endosomes traffic and mature is poorly understood. Here we find that a member of the reticulon protein family, Reticulon-3L (Rtn3L), concentrates ER-endosome MCSs as endosomes mature. We show that this localization is due to the long divergent N-terminal cytoplasmic domain of Rtn3L. We found that Rtn3L is recruited to ER-endosome MCSs by endosomal protein Rab9a, which marks a transition stage between early and late endosomes. Rab9a utilizes an FSV region to recruit Rtn3L via its six LC3-interacting region motifs. Consistent with our localization results, depletion or deletion of RTN3 from cells results in endosome maturation and cargo sorting defects, similar to RAB9A depletion. Together our data identify a tubular ER protein that promotes endosome maturation at ER MCSs. Wu and Voeltz characterize a tubular endoplasmic reticulum protein Reticulon-3L that is recruited to endosomes by Rab9a to coordinate endosome maturation.
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