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Regulation of transferrin recycling kinetics by PtdIns[4,5]P 2 availability
Author(s) -
Kim Sunyun,
Kim Hyunmyung,
Chang Belle,
Ahn Namhui,
Hwang Suha,
Di Paolo Gilbert,
Chang Sunghoe
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-4621fje
Subject(s) - endocytic cycle , endocytosis , microbiology and biotechnology , endosome , internalization , phosphatidylinositol , intracellular , phosphatidylinositol 4,5 bisphosphate , signal transduction , chemistry , transferrin receptor , biology , transferrin , cell , biochemistry
Phosphatidylinositol 4,5‐bisphosphate (PtdIns[4,5]P 2 ) 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]P 2 in endocytosis is well established, the precise trafficking steps relying on normal PtdIns[4,5]P 2 balance in the endosomal pathway have not yet been elucidated. Here we show that decrease in intracellular PtdIns[4,5]P 2 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]P 2 participates in multiple trafficking and/or sorting events during endocytosis. Coexpression of the PtdIns[4,5]P 2 synthesizing enzyme, PIP5KI, was able to rescue these endocytic defects. Furthermore, decreased levels of PtdIns[4,5]P 2 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]P 2 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. FASEB J. 20, E1753–E1762 (2006)