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Phosphoinositides, phospholipids that are key cell-signal mediators, are present at very low levels in cellular membranes and within nuclei. Phosphatidylinositol-(3,4,5)-trisphosphate (PIP3), a phosphoinositide barely present in resting cell membranes, is produced when cells receive either growth, proliferation, or movement signals. Aberrant PIP3 levels are associated with the formation of cancers. PIP3 pools are also present in the nucleus, specifically in the nucleolus. However, questions related to the organization and function of this lipid in such membraneless intranuclear structures remain unanswered. Therefore, chemical sensors for tracking cellular PIP3 are invaluable not only for timing signal initiation in membranes but also for identifying the organization and function of membraneless nuclear PIP3 pools. Because PIP3 is present in the inner leaflet of cell membranes and in the nucleus, cell-permeable, rapid-response fluorescent sensors would be ideal. We have designed two peptide-based, water-soluble, cell-permeable, ratiometric PIP3 sensors named as
Kundu et al. (Wed,) studied this question.
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