Regulation of transferrin recycling kinetics by PtdIns[4,5]P2 availability

FASEB J. 2006 Nov;20(13):2399-401. doi: 10.1096/fj.05-4621fje. Epub 2006 Sep 28.


Phosphatidylinositol 4,5-bisphosphate (PtdIns[4,5]P2) is a phosphoinositide involved in a variety of cellular functions, including signal transduction, organelle trafficking, and actin dynamics. Although the role of PtdIns[4,5]P2 in endocytosis is well established, the precise trafficking steps relying on normal PtdIns[4,5]P2 balance in the endosomal pathway have not yet been elucidated. Here we show that decrease in intracellular PtdIns[4,5]P2 levels achieved by the overexpression of the 5-phosphatase domain of synaptojanin 1 or by siRNA knock-down of PIP5Ks expression lead to severe defects in the internalization of transferrin as well as in the recycling of internalized transferrin back to the cell surface in COS-7 cells. These defects suggest that PtdIns[4,5]P2 participates in multiple trafficking and/or sorting events during endocytosis. Coexpression of the PtdIns[4,5]P2 synthesizing enzyme, PIP5KI gamma, was able to rescue these endocytic defects. Furthermore, decreased levels of PtdIns[4,5]P2 caused delays in rapid and slow membrane recycling pathways as well as a severe backup of endocytosed membrane. Taken together, our results demonstrate that PtdIns[4,5]P2 availability regulates multiple steps in the endocytic cycle in non-neuronal cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • COS Cells
  • Chlorocebus aethiops
  • Chromatography, Thin Layer
  • Endocytosis
  • Kinetics
  • Phosphatidylinositol 4,5-Diphosphate / metabolism*
  • Recombinant Proteins / metabolism
  • Transfection
  • Transferrin / metabolism*


  • Phosphatidylinositol 4,5-Diphosphate
  • Recombinant Proteins
  • Transferrin