Phospholipase C-related catalytically inactive protein regulates cytokinesis by protecting phosphatidylinositol 4,5-bisphosphate from metabolism in the cleavage furrow
Phospholipase C-related catalytically inactive protein regulates cytokinesis by protecting phosphatidylinositol 4,5-bisphosphate from metabolism in the cleavage furrow
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DOI：
10.1038/s41598-019-49156-3
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发表时间：
2019-09-04
影响因子：
4.6
通讯作者：
Kanematsu, Takashi
中科院分区：
文献类型：
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作者：
Asano, Satoshi;Ikura, Yasuka;Kanematsu, Takashi
胞质分裂是由卵裂沟的形成和侵入开始的。磷脂酰肌醇4，5-二磷酸[PI（4，5）P-2]积累后RhoA易位到卵裂沟是胞质分裂进行的先决条件。在这里，我们调查是否磷脂酶C（PLC）相关的催化失活蛋白（PRIP），PI（4，5）P-2的代谢调节剂，调节PI（4，5）P-2介导的胞质分裂。我们发现，PRIP定位于分裂沟在胞质分裂。此外，PRIP沉默的HeLa细胞表现出异常的胞质分裂。重要的是，PI（4，5）P-2在卵裂沟的积累，以及RhoA和磷酸肌球蛋白II调节轻链的卵裂沟的定位，在PR/P沉默细胞中减少。眼脑肾综合征Lowe-1（OCRL 1），一种磷脂酰肌醇-5-磷酸酶，在细胞中的过度表达降低了早期胞质分裂过程中PI（4，5）P-2的水平，并导致胞质分裂异常。然而，这些异常的胞质分裂表型通过PRIP的共表达而改善，但不通过PI（4，5）P-2未结合的PRIP突变体的共表达。总的来说，我们的研究结果表明，PRIP是在分裂沟，维持PI（4，5）P-2代谢和调节RhoA依赖的细胞质分裂的进展的组件。因此，我们认为PRIP正确地调节磷酸肌醇代谢，并介导正常的胞质分裂进程。
Cytokinesis is initiated by the formation and ingression of the cleavage furrow. Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P-2] accumulation followed by RhoA translocation to the cleavage furrow are prerequisites for cytokinesis progression. Here, we investigated whether phospholipase C (PLC)-related catalytically inactive protein (PRIP), a metabolic modulator of PI(4,5)P-2, regulates PI(4,5)P-2-mediated cytokinesis. We found that PRIP localised to the cleavage furrow during cytokinesis. Moreover, HeLa cells with silenced PRIP displayed abnormal cytokinesis. Importantly, PI(4,5)P-2 accumulation at the cleavage furrow, as well as the localisation of RhoA and phospho-myosin II regulatory light chain to the cleavage furrow, were reduced in PR/P-silenced cells. The overexpression of oculocerebrorenal syndrome of Lowe-1 (OCRL1), a phosphatidylinositol-5-phosphatase, in cells decreased PI(4,5)P-2 levels during early cytokinesis and resulted in cytokinesis abnormalities. However, these abnormal cytokinesis phenotypes were ameliorated by the co-expression of PRIP but not by co-expression of a PI(4,5)P-2-unbound PRIP mutant. Collectively, our results indicate that PRIP is a component at the cleavage furrow that maintains PI(4,5)P-2 metabolism and regulates RhoA-dependent progression of cytokinesis. Thus, we propose that PRIP regulates phosphoinositide metabolism correctively and mediates normal cytokinesis progression.