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Phosphoinositide metabolism in synaptic vesicle recycling Techniques in synaptic vesicle recycling

Phosphoinositide metabolism in synaptic vesicle recycling Techniques in synaptic vesicle recycling. Pre-. Vesicle reserve. Docking. Priming. Ca 2+. Fusion. Vesicle pools. SNARE complex. Munc-18. Munc-13.

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Phosphoinositide metabolism in synaptic vesicle recycling Techniques in synaptic vesicle recycling

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  1. Phosphoinositide metabolism in synaptic vesicle recycling Techniques in synaptic vesicle recycling

  2. Pre- Vesicle reserve Docking Priming Ca2+ Fusion Vesicle pools SNARE complex Munc-18 Munc-13 Morphologically, vesicles are classified as docked or undocked. Docked vesicles are further subdivided into primed and unprimed pools depending on whether they are competent to fuse when cells stimulated.

  3. SNARE complex and Ca2+ sensor

  4. Invagination Constriction Fission Uncoating Steps of clathrin-mediated endocytosis Splenv & De Camilli, 2000 • Invagination to create curvature. • Fission to separate the vesicle. • Uncoating to form a real vesicle.

  5. Endocytic invagination mediated by BAR-domain containing protein Peter et al., 2003

  6. Clathrin is critical to maintain the curvature of endocytic vesicle Hinrichsen et al., 2006

  7. Clathrin-mediated endocytosis Endocytic invagination • Bar-domain containing protein such as amphiphysin is critical for invagination by inducing membrane curvature • Clathrin, which is recruited by AP-2, is critical in maintaining the curvature of endocytic vesicles

  8. Dynamin is important for pinch-off of endocytic vesicle

  9. Reconstruction of dynamin 1 knockout synapse from electron tomography data.

  10. Synaptojanin 1 is critical for vesicle uncoating Hayashi et al., 2008

  11. Clathrin-mediated endocytosis Endocytic invagination Bar-domain containing protein such as amphiphysin which inducing membrane curvature Clathrin, which is recruited by AP-2, is critical in maintaining the curvature of endocytic vesicles Pinch-off: Dynamin Vesicle uncoating: Synaptojanin 1 that hydrolyzes PI(4,5)P2

  12. Clathrin-mediated endocytosis is a slow form of endocytosis

  13. Full fusion and kiss-and-run Harata et al, J Neurochem 2006

  14. Phosphoinositide metabolism in synaptic vesicle recycling Techniques in synaptic vesicle recycling

  15. PI(4,5)P2 concentrates on the plasma membrane PI(4,5)P2 PI(3,4,5)P3 PI(3)P PI(4)P PI(3,5)P2 PI(4,5)P2 • Functions of PI(4,5)P2: • Exocytosis and endocytosis • Ion channel regulation • Cell adhesion • Signal transduction • Actin polymerization/cell motility

  16. Coupling between PI(4,5)P2 metabolism and synaptic vesicle recycling phosphatases PI(4,5)P2PI(4)P Kinases PI(4)PPI(4,5)P2

  17. Ca2+ dependent interaction between synaptotagmin and PI(4,5)P2 Schiavo et al, PNAS 1996 Ca2+ Endocytosis.org

  18. PI(4)PPI(4,5)P2 Kinases Type I PI(4)P 5-kinase: phosphatases PIPK Iα PIPK Iβ PIPK Iγ PI(4,5)P2PI(4)P Kinases PI(4)PPI(4,5)P2 Coupling between PI(4,5)P2 metabolism and synaptic vesicle recycling

  19. Exocytosis defect in PIPK Iγ KO neuron mEPSCs in cultured neurons PIPK Iγ Di Paolo et al, Nature 2004

  20. Invagination Constriction Fission Uncoating Importance of lipids in endocytosis Splenv & De Camilli, 2000 • Invagination to create curvature. • Fission to separate the vesicle. • Uncoating to form a real vesicle.

  21. Synaptojanin 1 is a main phosphatase for PI(4,5)P2 metabolism in the brain WT Synaptojanin 1 Phosphatases KO Kinases PI(4,5)P2PI(4)P and PI PI(4)PPI(4,5)P2 Cremona et al. 1999 Cremona et al, Cell 1999 Synaptojanin 1 is critical for clathrin-mediated endocytosis presynaptically. PI(4,5)P2 metabolism is coupled to synaptic vesicle recycling

  22. Coupling between PI(4,5)P2 metabolism and synaptic vesicle recycling phosphatases PI(4,5)P2PI(4)P Kinases PI(4)PPI(4,5)P2

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