Title: Previously: Getting things made Now: getting them where they need to go: Protein Targeting
1Previously Getting things madeNow getting
them where they need to go Protein Targeting
Translation Converting nucleotide sequence to
amino acid chain
Role of tRNA, base pairing and wobble
Role of ribosome (A, P, E sites)
What happens after proteins are made?
2The Protein
What happens to the protein?
Folding
Sorting
What happens to the mRNA, the ribosomes the
tRNA?
Reuse
Polysomes
3Neurotransmitters synthesis and packaging
Where are neurotransmitters/neuropeptides
synthesized?
packaging
What must happen before they can be used?
transport
Barriers to packaging
Biological membrane of vesicle
Polar nature of neurotransmitter
How are the barriers overcome?
4Broad Idea Perhaps Bipolar is a result of
problem(s) getting the transmitters or the
receptors to the right place at the right
time?
How do we study this?--- examine what should
happen and look for changes from that standard
5Synaptic vesicles
What are they?
6Carrier Proteins
Why are they needed? How do they work? What kind
of energy is needed?
Main Classes Passive versus Active Transport
Going with or against the flow
Types of active transport Coupled ex.
symports or antiports Pumps like STE6, mdr,
Ca pump (ATP hydrolysis) Light driven pumps
(primarily bacterial)
Which class(es) likely to be used in initial
packaging of neurotransmitters? In their
re-uptake?
7Neurotransmitter receptor synthesis and packaging
Is a neurotransmitter receptor a cytosolic
protein?
Where is it synthesized? How does it get into a
membrane?
?
8Cytosolic vs. Noncytosolic proteins
The catecholamine theory of affective disorder
What sorts of situations could result in this
condition?
(what would alter the amount of signaling at a
synapse?)
1) Dont make enough neurotransmitter
2) Make it but dont package it into vesicles
or dont release it correctly
3) Make/ release but receptor not present on post
synaptic cell or not functioning correctly
4) Make/ Release/ Receptor there but overactive
re-uptake reduces the effective amount of
neurotransmitter
9Importance of specific translocation
gt50 of protein made on cytosolic ribosomes are
not intended to be used in the cytosol
Must cross between 1 and 3 membranes to reach
final destination
Mis-localization can have drastic
consequencesdisease or death
How does the cell know where to place a protein?
Cellular ZIP code
Signal Sequences and Signal Patches
10Signal sequences
How are these signals used?
Necessary and sufficient
11Targeting to the ER
If targeted to the ER where can a protein end up?
Main point of entry into the endomembrane
system Where euk. Membrane proteins become
membrane proteins (except for some mitochondrial
and chloroplast proteins)
TWO methods of targeting to ER
Minor pathway Sec-dependent translocation
Identified first in bacterial genetic screens
Post translational