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

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 rely...

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Bibliographic Details
Published in:The FASEB journal 2006-11, Vol.20 (13), p.2399-2401
Main Authors: Kim, Sunyun, Kim, Hyunmyung, Chang, Belle, Ahn, Namhui, Hwang, Suha, Di Paolo, Gilbert, Chang, Sunghoe
Format: Article
Language:English
Subjects:
Animals
Biological Transport
Cercopithecus aethiops
Chromatography, Thin Layer
COS Cells
Endocytosis
Kinetics
membrane recycling
Phosphatidylinositol 4,5-Diphosphate - metabolism
Recombinant Proteins - metabolism
Transfection
Transferrin - metabolism
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Summary: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, PIP5KIγ, 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.--Kim, S., Kim, H., Chang, B., Ahn, N., Hwang, S., Di Paolo, G., Chang, S. Regulation of transferrin recycling kinetics by PtdIns[4,5]P₂ availability.
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.05-4621fje