Cross-talk between miR-471-5p and autophagy component proteins regulates LC3-associated phagocytosis (LAP) of apoptotic germ cells.
Cross-talk between miR-471-5p and autophagy component proteins regulates LC3-associated phagocytosis (LAP) of apoptotic germ cells.
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DOI：
10.1038/s41467-017-00590-9
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发表时间：
2017-09-19
影响因子：
16.6
通讯作者：
Rao MK
中科院分区：
文献类型：
--
作者：
Panneerdoss S;Viswanadhapalli S;Abdelfattah N;Onyeagucha BC;Timilsina S;Mohammad TA;Chen Y;Drake M;Vuori K;Kumar TR;Rao MK
支持细胞对凋亡生殖细胞的吞噬清除对生殖细胞的发育和分化至关重要。在这里，使用组织特异性miRNA转基因小鼠模型，我们证明miR-471-5p和自噬成员蛋白之间的相互作用通过LC3相关吞噬作用(LAP)调节凋亡生殖细胞的清除。在Sertoli细胞中表达miR-471-5p的转基因小鼠显示生殖细胞凋亡增加，并损害男性生育能力。这些影响是由于缺陷的吞噬和LAP介导的对凋亡生殖细胞的清除受损，因为miR-471-5p转基因小鼠在支持细胞中显示出较低水平的Dock180、Lc3、Atg12、Becn1、Rab5和Rubcon。我们的结果表明，Dock180与自噬成员蛋白相互作用，构成一个功能依赖于LC3的吞噬复合体。我们发现雄激素通过控制miR-471-5p及其靶蛋白的表达来调节支持细胞的吞噬功能。这些发现表明，自噬机制的招募对于使用LAP有效清除支持细胞的凋亡生殖细胞是必不可少的。虽然支持细胞吞噬凋亡的生殖细胞是精子发生所必需的，但其机制却鲜为人知。在这里，作者展示了Sertoli细胞通过招募自噬成员蛋白来清除凋亡的生殖细胞，从而利用与LC3相关的吞噬作用(LAP)。
Phagocytic clearance of apoptotic germ cells by Sertoli cells is vital for germ cell development and differentiation. Here, using a tissue-specific miRNA transgenic mouse model, we show that interaction between miR-471-5p and autophagy member proteins regulates clearance of apoptotic germ cells via LC3-associated phagocytosis (LAP). Transgenic mice expressing miR-471-5p in Sertoli cells show increased germ cell apoptosis and compromised male fertility. Those effects are due to defective engulfment and impaired LAP-mediated clearance of apoptotic germ cells as miR-471-5p transgenic mice show lower levels of Dock180, LC3, Atg12, Becn1, Rab5 and Rubicon in Sertoli cells. Our results reveal that Dock180 interacts with autophagy member proteins to constitute a functional LC3-dependent phagocytic complex. We find that androgen regulates Sertoli cell phagocytosis by controlling expression of miR-471-5p and its target proteins. These findings suggest that recruitment of autophagy machinery is essential for efficient clearance of apoptotic germ cells by Sertoli cells using LAP. Although phagocytic clearance of apoptotic germ cells by Sertoli cells is essential for spermatogenesis, little of the mechanism is known. Here the authors show that Sertoli cells employ LC3-associated phagocytosis (LAP) by recruiting autophagy member proteins to clear apoptotic germ cells.
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DOI：
10.1073/pnas.90.19.9075
发表时间：
1993-10-01
影响因子：
11.1
作者：
ROTTER, V;SCHWARTZ, D;LEVINE, AJ
通讯作者：
LEVINE, AJ
影响因子：
3.6
作者：
Singh, Ajeet Pratap;Cummings, Connie A.;Archer, Trevor K.
通讯作者：
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DOI：
10.1073/pnas.0506084102
发表时间：
2005-11-15
影响因子：
11.1
作者：
Meng, J;Holdcraft, RW;Braun, RE
通讯作者：
Braun, RE
影响因子：
32.4
作者：
Henault J;Martinez J;Riggs JM;Tian J;Mehta P;Clarke L;Sasai M;Latz E;Brinkmann MM;Iwasaki A;Coyle AJ;Kolbeck R;Green DR;Sanjuan MA
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Sanjuan MA
影响因子：
2.2
作者：
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通讯作者：
Wang, Ping