Previously

1
Previously

• Hypotheses for molecular basis of bipolar
  disorder
• Suggest problem lies in protein targeting

The key player in neuronal transmission are
localized by Vesicular Traffic
Proteins made in cytosol
Sorting places proteins in membrane and in lumen
of organelles
Protein signal sequence directs sorting of that
protein
2 ex. Of Cellular machinery that recognizes
signal sequences
CBI 12.3 -- ribosome docked onto ER
2
ER proteins
ER
Where can a protein end up in the ER?
How does it get there?
What category do our neurotransmitter and
neurotransmitter receptor fall in?
3
Getting out of the ER
ER
Now what?
4
Vesicular traffic
Secretory pathway also method for delivering new
PM proteins
ER to Golgi to trans-Golgi network ? then
constitutive or regulated exocytosis
5
Constitutive and Regulated Exocytosis
Constitutive constant, sometimes called bulk
flow
Constitutive does not mean un-regulated
Regulated needs additional signal to initiate
fusion of vesicle with PM
6
Consequences of unregulated vesicular traffic
Mixing of organelle contents (? wont function
correctly)
Mislocalization of proteins (? wont function
correctly)
Inappropriate levels of secretion (too hi or too
lo)
A Dead Cell
7
Vesicular traffic control
Our neurotransmitter receptor need to go
through 5 cellular compartments before it gets
to the post synaptic membrane
How does a protein know what vesicle it should
be part of?
How does a vesicle know which membrane it
should go to?
How does it fuse when it gets there?
8
Stages of vesicle traffic
3 Stages Budding, targeting/docking and fusion
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Content selection
What goes inside which vesicle?
Lumenal protein
Transmembrane proteins
Combination of cytosolic and lumenal proteins
determine specific vesicle content
10
Budding
CBI 13.1 Clathrin
Fig 17-58
11
The SNARE hypothesis
V-SNARE
T-SNARE
Role of Rab proteins
retrograde
Fig 17-59
12
Synaptic vesicle fusion
VAMP
Syntaxin SNAP 25
Rab3a
Synaptotagmin
13
Transcytosis-Associated Protein (TAP)/p115