Fission yeast Opy1 is an endogenous PI(4,5)P sensor that binds to the phosphatidylinositol 4-phosphate 5-kinase Its3.

Phosphoinositides (PIPs) are a dynamic family of lipids that execute diverse roles in cell biology. PIP levels are regulated by numerous enzymes, but our understanding of how these enzymes are controlled in space and time is incomplete. One role of the PIP phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P] is to anchor the cytokinetic ring (CR) to the plasma membrane (PM) in While examining potential PI(4,5)P-binding proteins for roles in CR anchoring, we identified the dual pleckstrin homology (PH) domain-containing protein Opy1. Although related proteins are implicated in PIP regulation, we found no role for Opy1 in CR anchoring, which would be expected if it modulated PM PI(4,5)P levels. Our data indicate that although Opy1 senses PM PI(4,5)P levels and binds to the phosphatidylinositol 4-phosphate 5-kinase (PI5-kinase) Its3, Opy1 does not regulate Its3 kinase activity or PM PI(4,5)P levels, a striking difference from its homolog. However, overexpression of Opy1 resulted in cytokinesis defects, as might be expected if it sequestered PI(4,5)P Our results highlight the evolutionary divergence of dual PH domain-containing proteins and the need for caution when interpreting results based on their overexpression.This article has an associated First Person interview with the first author of the paper.