ARF6 stimulates clathrin/AP-2 recruitment to synaptic membranes by activating phosphatidylinositol phosphate kinase type Iγ

Clathrin-mediated endocytosis of synaptic vesicle membranes involves the recruitment of clathrin and AP-2 adaptor complexes to the presynaptic plasma membrane. Phosphoinositides have been implicated in nucleating coat assembly by directly binding to several endocytotic proteins including AP-2 and AP180. Here, we show that the stimulatory effect of ATP and GTPγS on clathrin coat recruitment is mediated at least in part by increased levels of PIP2. We also provide evidence for a role of ADP-ribosylation factor 6 (ARF6) via direct stimulation of a synaptically enriched phosphatidylinositol 4-phosphate 5-kinase type Iγ (PIPKIγ), in this effect. These data suggest a model according to which activation of PIPKIγ by ARF6-GTP facilitates clathrin-coated pit assembly at the synapse.

• Publication year

  2003

• Venue

  Journal of Cell Biology

• Publication date

  2003-07-07

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1083/jcb.200301006PMID 12847086PMCID 2172713
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Mechanism of ADP Ribosylation Factor-stimulated Phosphatidylinositol 4,5-Bisphosphate Synthesis in HL60 Cells*

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• Type I gamma phosphatidylinositol phosphate kinase targets and regulates focal adhesions.

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• ARF6-GTP recruits Nm23-H1 to facilitate dynamin-mediated endocytosis during adherens junctions disassembly

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• Dynamin at actin tails

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• Site-specific cross-linking reveals a differential direct interaction of class 1, 2, and 3 ADP-ribosylation factors with adaptor protein complexes 1 and 3.

  2002influential reference
• A phosphatidylinositol (4,5)-bisphosphate binding site within μ2-adaptin regulates clathrin-mediated endocytosis

  2002cited by this paper
• The large GTPase dynamin regulates actin comet formation and movement in living cells

  2002cited by this paper
• Molecular architecture and functional model of the endocytic AP2 complex.

  2002influential reference
• The yeast synaptojanin-like proteins control the cellular distribution of phosphatidylinositol (4,5)-bisphosphate.

  2002cited by this paper
• Impaired recycling of synaptic vesicles after acute perturbation of the presynaptic actin cytoskeleton

  2002cited by this paper
• Recruitment and regulation of phosphatidylinositol phosphate kinase type 1γ by the FERM domain of talin

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  2001cited by this paper
• Role of the ENTH domain in phosphatidylinositol-4,5-bisphosphate binding and endocytosis.

  2001cited by this paper
• Simultaneous binding of PtdIns(4,5)P2 and clathrin by AP180 in the nucleation of clathrin lattices on membranes.

  2001cited by this paper
• Differential binding of arfaptin 2/POR1 to ADP-ribosylation factors and Rac1.

  2001cited by this paper
• PIP kinase Igamma is the major PI(4,5)P(2) synthesizing enzyme at the synapse.

  2001cited by this paper
• Phosphoinositides, key molecules for regulation of actin cytoskeletal organization and membrane traffic from the plasma membrane.

  2001cited by this paper
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  2001cited by this paper
• A novel all helix fold of the AP180 amino-terminal domain for phosphoinositide binding and clathrin assembly in synaptic vesicle endocytosis.

  2001influential reference
• Phosphoinositides in membrane traffic at the synapse.

  2001cited by this paper
• Endocytic protein intersectin-l regulates actin assembly via Cdc42 and N-WASP

  2001cited by this paper
• Phosphatidylinositol 4,5-bisphosphate and Arf6-regulated membrane traffic

  2001influential reference
• Clathrin-mediated endocytosis: membrane factors pull the trigger.

  2001cited by this paper
• Accessory factors in clathrin-dependent synaptic vesicle endocytosis

  2000influential reference
• Mutations in Synaptojanin Disrupt Synaptic Vesicle Recycling

  2000influential reference
• Synaptojanin 2, a novel Rac1 effector that regulates clathrin-mediated endocytosis.

  2000cited by this paper
• Sequential steps in clathrin-mediated synaptic vesicle endocytosis.

  2000cited by this paper
• Molecular Links between Endocytosis and the Actin Cytoskeleton

  2000cited by this paper
• Fission and uncoating of synaptic clathrin-coated vesicles are perturbed by disruption of interactions with the SH3 domain of endophilin.

  2000cited by this paper
• Molecular Aspects of the Cellular Activities of ADP-Ribosylation Factors

  2000influential reference
• Actin Assembly at Membranes Controlled by ARF6

  2000cited by this paper
• AP-2 recruitment to synaptotagmin stimulated by tyrosine-based endocytic motifs.

  1999cited by this paper
• Phosphatidylinositol 4-Phosphate 5-Kinase a Is a Downstream Effector of the Small G Protein ARF 6 in Membrane Ruffle Formation 1984

  1999influential reference
• Phosphatidylinositol 4-phosphate 5-kinase alpha is a downstream effector of the small G protein ARF6 in membrane ruffle formation.

  1999cited by this paper
• Adp-Ribosylation Factor 6 and Endocytosis at the Apical Surface of Madin-Darby Canine Kidney Cells

  1999influential reference
• Synaptic vesicle biogenesis.

  1999cited by this paper
• A presynaptic role for the ADP ribosylation factor (ARF)-specific GDP/GTP exchange factor msec7-1.

  1999influential reference
• Phosphoinositide–Ap-2 Interactions Required for Targeting to Plasma Membrane Clathrin-Coated Pits

  1999cited by this paper
• Coupled Inositide Phosphorylation and Phospholipase D Activation Initiates Clathrin-coat Assembly on Lysosomes*

  1999cited by this paper
• ARF mediates recruitment of PtdIns-4-OH kinase-β and stimulates synthesis of PtdIns(4,5)P2 on the Golgi complex

  1999cited by this paper
• Deconstructing membrane traffic.

  1999cited by this paper
• Essential role of phosphoinositide metabolism in synaptic vesicle recycling.

  1999cited by this paper
• EFA6, a sec7 domain‐containing exchange factor for ARF6, coordinates membrane recycling and actin cytoskeleton organization

  1999cited by this paper
• ARF6 Targets Recycling Vesicles to the Plasma Membrane: Insights from an Ultrastructural Investigation

  1998cited by this paper
• Type I Phosphatidylinositol-4-phosphate 5-Kinases

  1998influential reference
• Synergistic Activation of Dynamin GTPase by Grb2 and Phosphoinositides*

  1998cited by this paper
• Subcellular Distribution and Differential Expression of Endogenous ADP-ribosylation Factor 6 in Mammalian Cells*

  1998influential reference
• Phosphatidylinositol-4,5-bisphosphate is required for endocytic coated vesicle formation.

  1998influential reference
• Direct and GTP-dependent interaction of ADP ribosylation factor 1 with coatomer subunit beta.

  1997cited by this paper
• The Actin Cytoskeleton Is Required for Receptor-mediated Endocytosis in Mammalian Cells*

  1997cited by this paper
• The Role of ADP-ribosylation Factor and Phospholipase D in Adaptor Recruitment

  1997influential reference
• A presynaptic inositol-5-phosphatase

  1996cited by this paper
• Intracellular Distribution of Arf Proteins in Mammalian Cells

  1996influential reference
• Evidence that phospholipase D mediates ADP ribosylation factor- dependent formation of Golgi coated vesicles

  1996cited by this paper
• The synaptic vesicle cycle: a single vesicle budding step involving clathrin and dynamin

  1996cited by this paper
• Synaptic vesicle proteins and early endosomes in cultured hippocampal neurons: differential effects of Brefeldin A in axon and dendrites

  1993cited by this paper
• ADP-ribosylation factor, a small GTP-dependent regulatory protein, stimulates phospholipase D activity.

  1993influential reference
• The binding of AP-1 clathrin adaptor particles to Golgi membranes requires ADP-ribosylation factor, a small GTP-binding protein.

  1993cited by this paper
• Biochemical dissection of AP-1 recruitment onto Golgi membranes

  1993cited by this paper
• ADP-ribosylation factor, a small GTP-binding protein, is required for binding of the coatomer protein beta-COP to Golgi membranes.

  1992cited by this paper
• Clathrin-coated vesicles in nervous tissue are involved primarily in synaptic vesicle recycling

  1992cited by this paper
• Recruitment of coat proteins onto Golgi membranes in intact and permeabilized cells: effects of brefeldin A and G protein activators.

  1992cited by this paper
• Protein N-myristoylation in Escherichia coli: reconstitution of a eukaryotic protein modification in bacteria.

  1990cited by this paper
• EVIDENCE FOR RECYCLING OF SYNAPTIC VESICLE MEMBRANE DURING TRANSMITTER RELEASE AT THE FROG NEUROMUSCULAR JUNCTION

  1973cited by this paper

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  2017cites this paper
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  2016cites this paper
• The multifaceted role of PIP2 in leukocyte biology

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  2015cites this paper
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  2015cites this paper
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  2015cites this paper
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  2015cites this paper
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  2015cites this paper
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  2013cites this paper
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  2013cites this paper
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  2013cites this paper
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