pathways of membrane trafficking some basic mechanisms and regulations
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Pathways of membrane trafficking
Visit URL htt : thierr . alli. ree. r isit URL
.trafficking particularly membrane fusion
2. In vivo mechanisms and regulatoryprocesses
Answers1. From genetics, and pharmacology and
2. From in vivo experiments
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B as i c m e c h a ni s m s f or i n t r a c e ll ul a r m e m b r an e t r a f f ic k i n g
Budding & fission
Fusion
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Membrane deformations durin buddin /fission
- -Negative curvature- favored by inverted cone-shaped lipids
1. The Golgi: a central1. The Golgi: a central platformplatform in membranein membranera c ngra c ng
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The Golgi is the central processing and sorting station of thesecretory pathway
ER ERGIC
ER ERGIC Golgi
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Vesicle & Maturation ModelsVesicle & Maturation Models
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3.3. FromFrom
SNAPsSNAPs totoSNAREsSNAREs
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SNAREs: tar ets of clostridial neurotoxinsSNAREs: tar ets of clostridial neurotoxins
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NSFNSF revisitedrevisited rolerole
..
(Sutton et al., Nature 1998)
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Jahn and Scheller Nature Reviews Molecular Cell Biology 7, 631643 (2006) | doi:10.1038/nrm2002
Jahn and Scheller Nature Reviews Molecular Cell Biology 7, 631643 (2006) | doi:10.1038/nrm2002
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SNAREs form 4SNAREs form 4--stranded coiledstranded coiled- -coil corecoil corecomplexcomplex
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SNARE: the generic modelSNARE: the generic model
Jahn and Scheller Nature Reviews Molecular Cell Biology 7, 631643 (2006) | doi:10.1038/nrm2002
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..
Membrane deformationsduring fusion
Negative curvature- favoredby inverted cone-shaped lipids
Positive curvature- favored-
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Annual Reviews
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Jahn and Scheller Nature Reviews Molecular Cell Biology 7, 631643 (2006) | doi:10.1038/nrm2002
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6.6. SNAREsSNAREs & membrane& membrane com artmentscom artmentsChane Levure Nmatode Drosophile Mammifres
SNAREs
21 23 20 35Qa
Syntaxines7 9 7 12
Nter SNAP25
Qc 6 4 5 8erR
V-SNARE5 6 5 9
Sec1 4 6 5 7Rab
Jahn and Scheller Nature Reviews Molecular Cell Biology 7, 631643 (2006) | doi:10.1038/nrm2002
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they are supposed to be?they are supposed to be?
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SeveralSeveral vv--SNAREsSNAREs interactinteract withwith molecularmolecularcoatscoats: VAMP4: VAMP4--AP1, VAMP7/TIAP1, VAMP7/TI- -VAMPVAMP--AP3AP3
e ong ne ong n oma noma n o ec , ,o ec , , - -VAMP/VAMP7VAMP/VAMP7 resemblesresembles a a domaindomain in AP2in AP2subunitssubunits
Tetanus NeurotoxinTetanus Neurotoxin- -Insensitive VesicleInsensitive Vesicle- -Associated Membrane Protein (TIAssociated Membrane Protein (TI- -
TITI--VAMP/VAMP7VAMP/VAMP7
XX--linked genelinked gene25kD v25kD v--SNARESNAREubiquitousubiquitous
NN--terminal extensionterminal extensionof 100aa calledof 100aa calledLonginongin domaindomain
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Tetanus neurotoxinTetanus neurotoxin sensitivesensitive andand insensitiveinsensitive exocytosisexocytosis
V-SNARENARE Sensitive to TeNTensitive to TeNT Expressed in neuronsxpressed in neurons
Synaptobrevin/VAMP2ynaptobrevin/VAMP2 Yeses Yeses
Cellubrevin/VAMP3ellubrevin/VAMP3 Yeses Noo
TII-VAMP/VAMP7AMP/VAMP7 Noo Yeses
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The Lon infamily
Ykt6 Sec22
TI-VAMP
SEDL 2SEDL, component of the transport protein particle (TRAPP)involved in endoplasmic reticulum-to-Golgi vesicle transport
Missense mutation X-linked spondyloepiphyseal dysplasia tarda
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TITI--VAMPVAMPinteractsinteracts withwith
--
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Plasma Membrane
AP-3
t-SNARE
Brevin v-SNARE
-
(+)(-)
Early/Recycling
Endosomes
Late Endosomes
/Lysosomes
TGN
+ Rapidly Exocytic
Compartment
CD63+ Slowly Exocytic
Compartment
AP3 is required to transport TI-VAMP to Late Endosomes
The mocha (mh ) mouse is a null mutant for AP3 ,ere ore as no comp ex n any ce ype
- - - coat and eye color dilutionreduced levels of renal l sosomalenzymes in the urineprolonged bleeding due to storagepool deficiency in the dense granulesof platelets.
(hypersynchronized) theta waveattern in the electrocorti ram.
ZnT3 and ClC-3 reduced in mossyfiber terminals
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-- uu
Lydia Danglot
Residual synaptic transmission after TeNT isasynchronous and AP-3 dependent
c t l + Te N T m o c h a + Te N T
c t l + Te N T
m o c h a + Te N T
A n i ta Sch eu b er, J ean -Ch r i s to p h e Po n cer
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TI-VAMP but not Syb2 is lost in mocha MF terminals
Lydia Danglo t
s t r a t u m o r ien s ( so ) s t r a t u m p y ramid a le ( sp ) s t r a t u m r ad ia tu m ( s r )s t r a t u m l u c i d u m ( s l u c ) s t r a t u m g r a n u l o s u m ( s g )
TI-VAMP is in the Golgi area of mocha granule cells
Lydia Danglo t
s t r a t u m o r ien s ( so ) s t r a t u m p y ramid a le ( sp ) s t r a t u m r ad ia tu m ( s r )s t r a t u m l u c i d u m ( s l u c ) s t r a t u m g r a n u l o s u m ( s g )
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PresynapticPresynaptic TITI--VAMPVAMP isis lostlost inin mocha mocha
AA formform ofof TeNTTeNT--resistantresistant asynchronousasynchronousre easere ease s s osos nn moc a moc a IncreasedIncreased basal release inbasal release in mocha mocha
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Regulation of TIRegulation of TI- -VAMPVAMP endocytosisendocytosis byby HrbHrb
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Regulation of TIRegulation of TI- -VAMPVAMP endocytosisendocytosis byby HrbHrb
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