Transcript Getting things where they need to go: Protein Targeting

Previously 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?
Targeting 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
Post-translational translocation
Sec- dependent
Co-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
Co-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”
So the protein can now be in the ER-*Where in the ER
and then what happens?
ER proteins
ER
Where can a protein end up in the ER? How does it get there?
Lumenal proteins
Single transmembrane span proteins
Multipass transmembrane proteins
What category do our neurotransmitter and
neurotransmitter receptor fall in?
Getting out of the ER
Golgi enzyme involved in glycosylation
Neurotransmitter
receptor
ER
Lysosomal acid hydrolase
Now what?
Vesicular traffic
Secretory pathway: also method for delivering new PM proteins
ER to Golgi to trans-Golgi network
 then constitutive or regulated exocytosis
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