TY - JOUR
T1 - An electrostatic switch displaces phosphatidylinositol phosphate kinases from the membrane during phagocytosis
AU - Fairn, Gregory D.
AU - Ogata, Koji
AU - Botelho, Roberto J.
AU - Stahl, Philip D.
AU - Anderson, Richard A.
AU - De Camilli, Pietro
AU - Meyer, Tobias
AU - Wodak, Shoshana
AU - Grinstein, Sergio
PY - 2009/11/30
Y1 - 2009/11/30
N2 - Plasmalemmal phosphatidylinositol (PI) 4,5-bisphosphate (PI4,5P 2) synthesized by PI 4-phosphate (PI4P) 5-kinase (PIP5K) is key to the polymerization of actin that drives chemotaxis and phagocytosis. We investigated the means whereby PIP5K is targeted to the membrane and its fate during phagosome formation. Homology modeling revealed that all PIP5K isoforms feature a positively charged face. Together with the substrate-binding loop, this polycationic surface is proposed to constitute a coincidence detector that targets PIP5Ks to the plasmalemma. Accordingly, manipulation of the surface charge displaced PIP5Ks from the plasma membrane. During particle engulfment, PIP5Ks detached from forming phagosomes as the surface charge at these sites decreased. Precluding the change in surface charge caused the PIP5Ks to remain associated with the phagosomal cup. Chemically induced retention of PIP5K-γ prevented the disappearance of PI4,5P2 and aborted phagosome formation. We conclude that a bistable electrostatic switch mechanism regulates the association/dissociation of PIP5Ks from the membrane during phagocytosis and likely other processes.
AB - Plasmalemmal phosphatidylinositol (PI) 4,5-bisphosphate (PI4,5P 2) synthesized by PI 4-phosphate (PI4P) 5-kinase (PIP5K) is key to the polymerization of actin that drives chemotaxis and phagocytosis. We investigated the means whereby PIP5K is targeted to the membrane and its fate during phagosome formation. Homology modeling revealed that all PIP5K isoforms feature a positively charged face. Together with the substrate-binding loop, this polycationic surface is proposed to constitute a coincidence detector that targets PIP5Ks to the plasmalemma. Accordingly, manipulation of the surface charge displaced PIP5Ks from the plasma membrane. During particle engulfment, PIP5Ks detached from forming phagosomes as the surface charge at these sites decreased. Precluding the change in surface charge caused the PIP5Ks to remain associated with the phagosomal cup. Chemically induced retention of PIP5K-γ prevented the disappearance of PI4,5P2 and aborted phagosome formation. We conclude that a bistable electrostatic switch mechanism regulates the association/dissociation of PIP5Ks from the membrane during phagocytosis and likely other processes.
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U2 - 10.1083/jcb.200909025
DO - 10.1083/jcb.200909025
M3 - Article
C2 - 19951917
AN - SCOPUS:74049118478
SN - 0021-9525
VL - 187
SP - 701
EP - 714
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 5
ER -