PMID- 19951917
OWN - NLM
STAT- MEDLINE
DCOM- 20100114
LR  - 20211020
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 187
IP  - 5
DP  - 2009 Nov 30
TI  - An electrostatic switch displaces phosphatidylinositol phosphate kinases from the 
      membrane during phagocytosis.
PG  - 701-14
LID - 10.1083/jcb.200909025 [doi]
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-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.
FAU - Fairn, Gregory D
AU  - Fairn GD
AD  - Program in Cell Biology and 2 Structural Biology Program, Hospital for Sick 
      Children, Toronto, Ontario, Canada M5G1X8.
FAU - Ogata, Koji
AU  - Ogata K
FAU - Botelho, Roberto J
AU  - Botelho RJ
FAU - Stahl, Philip D
AU  - Stahl PD
FAU - Anderson, Richard A
AU  - Anderson RA
FAU - De Camilli, Pietro
AU  - De Camilli P
FAU - Meyer, Tobias
AU  - Meyer T
FAU - Wodak, Shoshana
AU  - Wodak S
FAU - Grinstein, Sergio
AU  - Grinstein S
LA  - eng
GR  - P30 DA018343/DA/NIDA NIH HHS/United States
GR  - R01 GM030179/GM/NIGMS NIH HHS/United States
GR  - R01 GM030179-27/GM/NIGMS NIH HHS/United States
GR  - 7075/CAPMC/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Minor Histocompatibility Antigens)
RN  - 0 (Phospholipids)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.67 (phosphatidylinositol phosphate 4-kinase)
RN  - EC 2.7.1.68 (1-phosphatidylinositol-4-phosphate 5-kinase)
SB  - IM
MH  - Animals
MH  - Cell Membrane/*enzymology
MH  - Macrophages
MH  - Mice
MH  - Minor Histocompatibility Antigens
MH  - Models, Molecular
MH  - *Phagocytosis
MH  - Phospholipids/metabolism
MH  - Phosphotransferases (Alcohol Group Acceptor)/chemistry/*metabolism
MH  - Protein Transport
MH  - Sequence Homology, Amino Acid
MH  - Static Electricity
PMC - PMC2806594
EDAT- 2009/12/03 06:00
MHDA- 2010/01/15 06:00
PMCR- 2010/05/30
CRDT- 2009/12/03 06:00
PHST- 2009/12/03 06:00 [entrez]
PHST- 2009/12/03 06:00 [pubmed]
PHST- 2010/01/15 06:00 [medline]
PHST- 2010/05/30 00:00 [pmc-release]
AID - jcb.200909025 [pii]
AID - 200909025 [pii]
AID - 10.1083/jcb.200909025 [doi]
PST - ppublish
SO  - J Cell Biol. 2009 Nov 30;187(5):701-14. doi: 10.1083/jcb.200909025.