Casein Kinase 1 Family Member CK1δ/Hrr25 Is Required for Autophagosome Completion

Casein Kinase 1 Family Member CK1δ/Hrr25 Is Required for Autophagosome Completion
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自噬体完成需要酪蛋白激酶 1 家族成员 CK1 delta/Hrr25

DOI:
10.3389/fcell.2020.00460
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发表时间:
2020-07-07
影响因子:
5.5
通讯作者:
Wang, Juan
Wang, Juan
中科院分区:
生物学2区
文献类型:
--
作者:
Li, Yuting;Chen, Xuechai;Wang, Juan

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自噬始于隔离膜的启动和成核,进一步扩展和密封形成自噬体。隔离膜关闭的调节仍然知之甚少。 CK1 delta 是丝氨酸/苏氨酸特异性激酶酪蛋白激酶 I 家族的成员。尽管据报道 CK1 delta 参与多种细胞过程,但其在自噬中的作用尚不清楚。在这里,我们发现 CK1 delta 调节自噬从隔离膜形成到自噬体闭合的进程,并且对于巨自噬至关重要。 CK1 delta 缺失会导致自噬通量受损和未密封隔离膜的积累。发现 LC3 与 ATG9A、ATG14L 和 ATG16L1 的关联在 CK1 delta 耗尽的细胞中增加。 CK1 delta 在自噬体完成中的作用似乎在酵母和人类之间是保守的。我们的数据揭示了 CK1 delta/Hrr25 在自噬体完成中的关键作用。
Autophagy starts with the initiation and nucleation of isolation membranes, which further expand and seal to form autophagosomes. The regulation of isolation membrane closure remains poorly understood. CK1 delta is a member of the casein kinase I family of serine/threonine specific kinases. Although CK1 delta is reported to be involved in various cellular processes, its role in autophagy is unknown. Here, we show that CK1 delta regulates the progression of autophagy from the formation of isolation membranes to autophagosome closure, and is essential for macroautophagy. CK1 delta depletion results in impaired autophagy flux and the accumulation of unsealed isolation membranes. The association of LC3 with ATG9A, ATG14L, and ATG16L1 was found to be increased in CK1 delta-depleted cells. The role of CK1 delta in autophagosome completion appears to be conserved between yeasts and humans. Our data reveal a key role for CK1 delta/Hrr25 in autophagosome completion.