Phospholipase C-related catalytically inactive protein regulates cytokinesis by protecting phosphatidylinositol 4,5-bisphosphate from metabolism in the cleavage furrow

• Published in: Scientific reports Vol. 9; no. 1; pp. 12729 - 14
• Main Authors: Asano, Satoshi, Ikura, Yasuka, Nishimoto, Mitsuki, Yamawaki, Yosuke, Hamao, Kozue, Kamijo, Keiju, Hirata, Masato, Kanematsu, Takashi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04-09-2019; Nature Publishing Group
• Subjects: 14/19; 14/63; 38; 38/89; 42; 631/45/287/1194; 631/80/641/2090; 82; 82/1; 96; 96/21; 96/95; Cell Membrane - genetics; Cell Membrane - metabolism; Cytokinesis; Embryos; Furrows; HeLa Cells; Humanities and Social Sciences; Humans; Invertebrates; Metabolism; multidisciplinary; Myosin; Phenotypes; Phosphatidylinositol 4,5-diphosphate; Phosphatidylinositol 4,5-Diphosphate - metabolism; Phosphoinositide Phospholipase C - genetics; Phosphoinositide Phospholipase C - metabolism; Phospholipase C; Phosphoric Monoester Hydrolases - genetics; Phosphoric Monoester Hydrolases - metabolism; RhoA protein; Science; Science (multidisciplinary); Translocation
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-49156-3

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
PRIP
-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.