An electrostatic switch displaces phosphatidylinositol phosphate kinases from the membrane during phagocytosis.
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-gamma prevented the disappearance of PI4,5P(2) 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.
Fairn
Gregory D
GD
Program in Cell Biology and 2 Structural Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada M5G1X8.
Ogata
Koji
K
Botelho
Roberto J
RJ
Stahl
Philip D
PD
Anderson
Richard A
RA
De Camilli
Pietro
P
Meyer
Tobias
T
Wodak
Shoshana
S
Grinstein
Sergio
S
D000818:Animals; D002462:Cell Membrane / Q000201:enzymology*; D008264:Macrophages; D051379:Mice; D015778:Minor Histocompatibility Antigens; D008958:Models, Molecular; D010587:Phagocytosis; D010743:Phospholipids / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry / Q000378:metabolism*; D021381:Protein Transport; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity
D015778:Minor Histocompatibility Antigens; D010743:Phospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); C402182:phosphatidylinositol phosphate 4-kinase; C020077:1-phosphatidylinositol-4-phosphate 5-kinase