PMID- 16843639
OWN - NLM
STAT- MEDLINE
DCOM- 20070410
LR  - 20131121
IS  - 0898-6568 (Print)
IS  - 0898-6568 (Linking)
VI  - 19
IP  - 1
DP  - 2007 Jan
TI  - Signalling through phospholipase C interferes with clathrin-mediated endocytosis.
PG  - 42-51
AB  - We investigated if phosphatidylinositol(4,5)bisphosphate (PtdIns(4,5)P2) 
      hydrolysis by phospholipase C activation through cell surface receptors would 
      interfere with clathrin-mediated endocytosis as recruitment of clathrin assembly 
      proteins is PtdIns(4,5)P2-dependent. In the WKPT renal epithelial cell line, 
      endocytosed insulin and beta2-glycoprotein I (beta2gpI) were observed in separate 
      compartments, although endocytosis of both ligands was clathrin-dependent as 
      demonstrated by expression of the clathrin-binding C-terminal domain of AP180 
      (AP180-C). The two uptake mechanisms were different as only insulin uptake was 
      reduced when the mu2-subunit of the adaptor complex AP-2 was silenced by RNA 
      interference. ATP receptors are expressed at the apical surface of renal cells 
      and, thus, we examined the effect of extracellular ATP on insulin and beta2gpI 
      uptake. ATP stimulated phospholipase C activity, and also suppressed uptake of 
      insulin, but not beta2gpI. This effect was reversed by the PLC inhibitor U-73122. 
      In polarized cell cultures, insulin uptake was apical, whereas beta2gpI uptake 
      was through the basolateral membrane, thus providing an explanation for selective 
      inhibition of insulin endocytosis by ATP. Taken together, these results 
      demonstrate that stimulation of apical G-protein-coupled P2Y receptors, which are 
      coupled to phospholipase C activation diminishes clathrin-mediated endocytosis 
      without interfering with basolateral endocytic mechanisms.
FAU - Carvou, Nicolas
AU  - Carvou N
AD  - Department of Physiology, University College London, London WC1E 6JJ UK.
FAU - Norden, Anthony G W
AU  - Norden AG
FAU - Unwin, Robert J
AU  - Unwin RJ
FAU - Cockcroft, Shamshad
AU  - Cockcroft S
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060606
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (Clathrin)
RN  - 0 (Estrenes)
RN  - 0 (Insulin)
RN  - 0 (Monomeric Clathrin Assembly Proteins)
RN  - 0 (Pyrrolidinones)
RN  - 0 (Receptors, Purinergic P2)
RN  - 0 (Transcription Factor AP-2)
RN  - 0 (beta 2-Glycoprotein I)
RN  - 0 (clathrin assembly protein AP180)
RN  - 112648-68-7 
      (1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.- (phosphatidylinositol 4,5-biphosphate kinase)
RN  - EC 3.1.4.- (Type C Phospholipases)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Cell Line
MH  - Clathrin/*physiology
MH  - *Endocytosis
MH  - Enzyme Activation
MH  - Epithelial Cells/physiology
MH  - Estrenes/pharmacology
MH  - Insulin/metabolism
MH  - Monomeric Clathrin Assembly Proteins/metabolism
MH  - Phosphotransferases (Alcohol Group Acceptor)/metabolism
MH  - Protein Structure, Tertiary
MH  - Pyrrolidinones/pharmacology
MH  - Rats
MH  - Receptors, Purinergic P2/metabolism
MH  - Signal Transduction
MH  - Transcription Factor AP-2/metabolism
MH  - Type C Phospholipases/antagonists & inhibitors/*physiology
MH  - Urothelium/cytology
MH  - beta 2-Glycoprotein I/metabolism
EDAT- 2006/07/18 09:00
MHDA- 2007/04/11 09:00
CRDT- 2006/07/18 09:00
PHST- 2006/02/03 00:00 [received]
PHST- 2006/05/23 00:00 [revised]
PHST- 2006/05/24 00:00 [accepted]
PHST- 2006/07/18 09:00 [pubmed]
PHST- 2007/04/11 09:00 [medline]
PHST- 2006/07/18 09:00 [entrez]
AID - S0898-6568(06)00133-1 [pii]
AID - 10.1016/j.cellsig.2006.05.023 [doi]
PST - ppublish
SO  - Cell Signal. 2007 Jan;19(1):42-51. doi: 10.1016/j.cellsig.2006.05.023. Epub 2006 
      Jun 6.