Mitotic phosphorylation of VCIP135 blocks p97ATPase-mediated Golgi membrane fusion.
Mitotic phosphorylation of VCIP135 blocks p97ATPase-mediated Golgi membrane fusion.
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DOI：
10.1016/j.bbrc.2013.02.090
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发表时间：
2013-04
影响因子：
3.1
通讯作者：
G. Totsukawa;Ayaka Matsuo;Ayano Kubota;Yuya Taguchi;Hisao Kondo
中科院分区：
文献类型：
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作者：
G. Totsukawa;Ayaka Matsuo;Ayano Kubota;Yuya Taguchi;Hisao Kondo
在哺乳动物中，高尔基体在有丝分裂早期被分解，并在有丝分裂结束时重新组装。对于高尔基体解体，膜融合需要被阻断。高尔基体的生物发生需要两个不同的p97 ATP酶介导的膜融合，p97/p47和p97/p37途径。我们先前报道了丝氨酸-140上的p47磷酸化和丝氨酸-56和苏氨酸-59上的p37磷酸化分别导致p97/p47和p97/p37途径的有丝分裂抑制[11，14]。在这项研究中，我们显示了另一种机制的有丝分裂抑制p97介导的高尔基体膜融合。我们阐明了VCIP 135是两种p97膜融合途径中的必需因子，在有丝分裂时被Cdc 2在苏氨酸-760和丝氨酸-767上磷酸化，并且这种磷酸化的VCIP 135不与p97结合。体外高尔基体重组试验显示，模拟有丝分裂磷酸化的VCIP 135（T760 E，S767 E）不会引起脑池再生。我们的研究结果表明，在有丝分裂中，Threatinine-760和Serine-767上的VCIP 135磷酸化抑制p97介导的高尔基体膜融合。
In mammals, the Golgi apparatus is disassembled early mitosis and reassembled at the end of mitosis. For Golgi disassembly, membrane fusion needs to be blocked. Golgi biogenesis requires two distinct p97ATPase-mediated membrane fusion, the p97/p47 and p97/p37 pathways. We previously reported that p47 phosphorylation on Serine-140 and p37 phosphorylation on Serine-56 and Threonine-59 result in mitotic inhibition of the p97/p47 and the p97/p37 pathways, respectively [11,14]. In this study, we show another mechanism of mitotic inhibition of p97-mediated Golgi membrane fusion. We clarified that VCIP135, an essential factor in both p97 membrane fusion pathways, is phosphorylated on Threonine-760 and Serine-767 by Cdc2 at mitosis and that this phosphorylated VCIP135 does not bind to p97. An in vitro Golgi reassembly assay revealed that VCIP135(T760E, S767E), which mimics mitotic phosphorylation, caused no cisternal regrowth. Our results indicate that the phosphorylation of VCIP135 on Threonine-760 and Serine-767 inhibits p97-mediated Golgi membrane fusion at mitosis.