Nuclear Translocation of Phospholipase C-δ1 Is Linked to the Cell Cycle and Nuclear Phosphatidylinositol 4,5-Bisphosphate

• Published in: The Journal of biological chemistry 2005-06, Vol.280 (23), p.22060-22069
• Main Authors: Stallings, Jonathan D., Tall, Edward G., Pentyala, Srinivas, Rebecchi, Mario J.
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M413813200

Nuclear phosphoinositides, especially phosphatidylinositol 4,5-bisphosphate, fluctuate throughout the cell cycle and are linked to proliferation and differentiation. Here we report that phospholipase C-δ1 accumulates in the nucleus at the G1/S boundary and in G0 phases of the cell cycle. Furthermore, as wild-type protein accumulated in the nucleus, nuclear phosphatidylinositol 4,5-bisphosphate levels were elevated 3–5-fold, whereas total levels were decreased compared with asynchronous cultures. To test whether phosphatidylinositol 4,5-bisphosphate binding is important during this process, we introduced a R40D point mutation within the pleckstrin homology domain of phospholipase C-δ1, which disables high affinity phosphatidylinositol 4,5-bisphosphate binding, and found that nuclear translocation was significantly reduced at G1/S and in G0. These results demonstrate a cell cycle-dependent compartmentalization of phospholipase C-δ1 and support the idea that relative levels of phosphoinositides modulate the portioning of phosphoinositide-binding proteins between the nucleus and other compartments.