Title: Phosphoinositide metabolism in synaptic vesicle recycling
1- Phosphoinositide metabolism in synaptic vesicle
recycling - Techniques in synaptic vesicle recycling
2Vesicle pools
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.
3SNARE complex and Ca2 sensor
4Steps of clathrin-mediated endocytosis
Splenv De Camilli, 2000
- Invagination to create curvature.
- Fission to separate the vesicle.
- Uncoating to form a real vesicle.
5Endocytic invagination mediated by BAR-domain
containing protein
6Clathrin is critical to maintain the curvature of
endocytic vesicle
Hinrichsen et al., 2006
7Clathrin-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
8Dynamin is important for pinch-off of endocytic
vesicle
9Reconstruction of dynamin 1 knockout synapse from
electron tomography data.
10Synaptojanin 1 is critical for vesicle uncoating
Hayashi et al., 2008
11Clathrin-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
12Clathrin-mediated endocytosis is a slow form of
endocytosis
13Full fusion and kiss-and-run
Harata et al, J Neurochem 2006
14- Phosphoinositide metabolism in synaptic vesicle
recycling - Techniques in synaptic vesicle recycling
15PI(4,5)P2 concentrates on the plasma membrane
PI(4,5)P2
- Functions of PI(4,5)P2
- Exocytosis and endocytosis
- Ion channel regulation
- Cell adhesion
- Signal transduction
- Actin polymerization/cell motility
16Coupling between PI(4,5)P2 metabolism and
synaptic vesicle recycling
17Ca2 dependent interaction between synaptotagmin
and PI(4,5)P2
Schiavo et al, PNAS 1996
18Coupling between PI(4,5)P2 metabolism and
synaptic vesicle recycling
19Exocytosis defect in PIPK I? KO neuron
Di Paolo et al, Nature 2004
20Importance of lipids in endocytosis
Splenv De Camilli, 2000
- Invagination to create curvature.
- Fission to separate the vesicle.
- Uncoating to form a real vesicle.
21PI(4,5)P2 metabolism is coupled to synaptic
vesicle recycling
22Coupling between PI(4,5)P2 metabolism and
synaptic vesicle recycling