Pathways of Membrane Trafficking Some Basic Mechanisms and Regulations

8/14/2019 Pathways of Membrane Trafficking Some Basic Mechanisms and Regulations

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Pathways of membrane trafficking

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.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



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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



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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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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



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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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Pathways of Membrane Trafficking Some Basic Mechanisms and Regulations