Phosphoinositide Diversity, Distribution, and Effector Function: Stepping Out of the Box

Bioessays. 2017 Dec;39(12). doi: 10.1002/bies.201700121. Epub 2017 Oct 4.


Phosphoinositides (PtdInsPs) modulate a plethora of functions including signal transduction and membrane trafficking. PtdInsPs are thought to consist of seven interconvertible species that localize to a specific organelle, to which they recruit a set of cognate effector proteins. Here, in reviewing the literature, we argue that this model needs revision. First, PtdInsPs can carry a variety of acyl chains, greatly boosting their molecular diversity. Second, PtdInsPs are more promiscuous in their localization than is usually acknowledged. Third, PtdInsP interconversion is likely achieved through kinase-phosphatase enzyme complexes that coordinate their activities and channel substrates without affecting bulk substrate population. Additionally, we contend that despite hundreds of PtdInsP effectors, our attention is biased toward few proteins. Lastly, we recognize that PtdInsPs can act to nucleate coincidence detection at the effector level, as in PDK1 and Akt. Overall, better integrated models of PtdInsP regulation and function are not only possible but needed.

Keywords: cellular organization; eukaryotes; lipids; membranes; organelles; phosphoinositides; protein-lipid interactions.

Publication types

  • Review

MeSH terms

  • 1-Phosphatidylinositol 4-Kinase / genetics*
  • 1-Phosphatidylinositol 4-Kinase / metabolism
  • 3-Phosphoinositide-Dependent Protein Kinases / genetics
  • 3-Phosphoinositide-Dependent Protein Kinases / metabolism
  • Acylation
  • Animals
  • Cell Compartmentation
  • Eukaryotic Cells / cytology
  • Eukaryotic Cells / metabolism*
  • Gene Expression Regulation
  • Intracellular Membranes / metabolism*
  • Phosphatidylinositols / chemistry
  • Phosphatidylinositols / classification
  • Phosphatidylinositols / metabolism*
  • Phosphoinositide Phosphatases / genetics*
  • Phosphoinositide Phosphatases / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction


  • Phosphatidylinositols
  • 1-Phosphatidylinositol 4-Kinase
  • 3-Phosphoinositide-Dependent Protein Kinases
  • PDPK1 protein, human
  • Proto-Oncogene Proteins c-akt
  • Phosphoinositide Phosphatases