PI(4,5)P2: signaling the plasma membrane

In the almost 70 years since the first hints of its existence, the phosphoinositide, phos-phatidyl-D-myo-inositol 4,5-bisphosphate has been found to be central in the biological regulation of plasma membrane (PM) function. Here, we provide an overview of the sig-naling, transport and structural roles the lipid plays at the cell surface in animal cells. These include being substrate for second messenger generation, direct modulation of receptors, control of membrane traffic, regulation of ion channels and transporters, and modulation of the cytoskeleton and cell polarity. We conclude by re-evaluating PI(4,5)P2's designation as a signaling molecule, instead proposing a cofactor role, enabling PM -selective function for many proteins.

Automated summary

This article provides an overview of the various roles of phosphoinositide, phos-phatidyl-D-myo-inositol 4,5-bisphosphate (PI(4,5)P2) at the cell surface in animal cells, including its involvement in signaling, transport, and structural functions. PI(4,5)P2 plays a central role in the biological regulation of plasma membrane function and is involved in multiple processes such as second messenger generation, receptor modulation, and membrane traffic control. Furthermore, the article proposes a cofactor role for PI(4,5)P2, enabling selective plasma membrane function for many proteins.