Title: Previously Bio308
1Previously Bio308
- Hypotheses for molecular basis of bipolar
disorder - Suggest problem lies in protein targeting
Proteins made in cytosol (cytosolic and membrane
ones)
Sorting places proteins in membrane and in lumen
of organelles Routing controlled by the
presence or absence of targeting Information in
the primary structure (the amino acid
sequence) of the protein itself
But first what type of transport (general class
and specific type) is used to get
neurotransmitters into synaptic vesicles?
2Targeting to the ER
If targeted to the ER where can a protein end up?
Main point of entry into the endomembrane system
TWO methods of targeting to ER
Minor pathway Sec-dependent translocation
Identified first in bacterial genetic screens
Post translational
3Post-translational translocation
Sec- dependent
4Co-translational translocation
Major pathway SRP-dependent translocation
First identified in in vitro experiments using
canine microsomes and wheat germ translation
systems
Co-translational
CBI 12.3
5Co-translational translocation
Important components from ER SRP- receptor,
TRAM Sec61 complex ( BiP/Kar2-- sometimes)
Mammals ER translocation involves push Yeast
ER translocation involves push and pull
6So the protein can now be in the ER--
Where in the ER and then what happens?
7ER 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?
8Getting out of the ER
ER
Now what?
9Vesicular traffic
Secretory pathway also method for delivering new
PM proteins
ER to Golgi to trans-Golgi network ? then
constitutive or regulated exocytosis
10Constitutive 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