PARP1-produced poly-ADP-ribose causes the PARP12 translocation to stress granules and impairment of Golgi complex functions.
PARP1-produced poly-ADP-ribose causes the PARP12 translocation to stress granules and impairment of Golgi complex functions.
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DOI：
10.1038/s41598-017-14156-8
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发表时间：
2017-10-25
影响因子：
4.6
通讯作者：
Corda D
中科院分区：
文献类型：
--
作者：
Catara G;Grimaldi G;Schembri L;Spano D;Turacchio G;Lo Monte M;Beccari AR;Valente C;Corda D
聚ADP核糖聚合酶（PARP）1和2是催化核蛋白的聚ADP核糖基化的核酶，其将聚ADP核糖（PAR）聚合物转移到特定残基。PARP和PAR参与多种功能，包括细胞核中的DNA修复和细胞质中的应激颗粒组装。应激颗粒通过聚集和稳定mRNA以及几种胞质PARP和信号蛋白来调节翻译以调节细胞代谢和存活。我们的研究集中在这些PARP之一，PARP 12，高尔基体定位的单ADP核糖基转移酶，在压力挑战下可逆地从高尔基体复合体易位到压力颗粒。PARP 1的激活和核PAR的释放通过PAR与PARP 12-WWE结构域的直接结合来驱动这种易位。因此，PAR的形成在功能上联系的活动，核和胞质PARP在应激反应，决定释放的PARP 12从高尔基复合体和解体的高尔基膜，然后在顺行膜交通的块。值得注意的是，这些功能可以通过恢复应激状态（通过药物洗脱）来挽救。总之，这些数据指向一种新的、可逆的核信号传导，该信号传导感测应激，然后作用于胞质PARP 12，这反过来将应激反应转化为细胞内膜交通的可逆阻断。
Poly-ADP-ribose-polymerases (PARPs) 1 and 2 are nuclear enzymes that catalyze the poly-ADP-ribosylation of nuclear proteins transferring poly-ADP-ribose (PAR) polymers to specific residues. PARPs and PAR intervene in diverse functions, including DNA repair in the nucleus and stress granule assembly in the cytoplasm. Stress granules contribute to the regulation of translation by clustering and stabilizing mRNAs as well as several cytosolic PARPs and signaling proteins to modulate cell metabolism and survival. Our study is focused on one of these PARPs, PARP12, a Golgi-localized mono-ADP-ribosyltransferase that under stress challenge reversibly translocates from the Golgi complex to stress granules. PARP1 activation and release of nuclear PAR drive this translocation by direct PAR binding to the PARP12-WWE domain. Thus, PAR formation functionally links the activity of the nuclear and cytosolic PARPs during stress response, determining the release of PARP12 from the Golgi complex and the disassembly of the Golgi membranes, followed by a block in anterograde-membrane traffic. Notably, these functions can be rescued by reverting the stress condition (by drug wash-out). Altogether these data point at a novel, reversible nuclear signaling that senses stress to then act on cytosolic PARP12, which in turn converts the stress response into a reversible block in intracellular-membrane traffic.
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发表时间：
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影响因子：
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作者：
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