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Lecture 5 (endoplasmic reticulum part 2)

The ER is responsible for the synthesis of lipids and after the lipid has been synthesized they are
enveloped in a single leaflet vesicle and it goes to the cytoplasm as a lipid droplet
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The rough ER is responsible for synthesizing
secretory proteins and also membrane protein
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Eventually they are transported by secretory vesicles
to whatever destination they are suppose to go
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Well ribosomes are not always on the ER, they can be free
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So these cytosolic
proteins depending on their signal peptide will eventually find their way to their target insert into the
target membrane and into the lumen of their target membrane
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Its
not that difficult you have cell
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Well when the membranes are disrupted they will
tend to form micelles, well if you use the gradient centrifugation with sucrose and spin it
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Now the smaller microsomes have a problem, they are really a mixture you have smooth ER,
plasma membrane, golgi membrane, mitochondrial membrane all mixed
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ER is a very important storage site for calcium ions
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In the case where calcium is needed it can travel
from the inside of the lumen to the outside via calcium channels
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Calcium ion when increased intracellularly will cause the contraction of muscle
fibers
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Also when you are trying to store calcium in the
ER, you are going from a low concentration to a high concentration gradient
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Going back to protein synthesis
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Lets break the process down into different segements: lets first talk about the synthesis of secretory
proteins
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When
they are bound together there is a channel that forms a channel and this is where the mrNA goes right
through
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tRNA are floating in the cytosol and tRNA
are connected to amino acids
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Now

in the mRNA we know that there are codons and you have tRNA that contain anti-codons
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What happens then when a ribosome has this synthesis of peptides started? Your first sequence is
usually 6-8 hydrophobic amino acids
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So the sequence comes out
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Now how does this complex find its way to the ER
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Well the complex is brought to the ER by SRP(signal
recongnition particle)
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Well the
SRP is a protein that floats around in the cytosol
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So when this complex is formed only when
you have the mrNA , tRNA, RNA and the signal sequence can the SRP bind to it
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After this complex binds to the
SRP, translation stops
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It has specificity to the signal recognition
particle only after the SRP has been bound to the ribosomal complex
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So what is the translocator protein
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Well the binding of this whole
complex with the SRP receptor , what happens is that it will align this whole complex with the
translocator protein
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The SRP binds to the signal
recognition particle but the receptor brings it to a point where the ribosome will bind to the protein
membrane of the ER membrane
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And there is a pore in the membrane
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If the signal sequence binds to the
translocator protein, then all of a sudden between the ribosome and the translocator protein and the
ribosome you have a continuous channel
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Now this passage will not appear until the signal peptide sequence binds
to the translocator protein
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And the signal sequence as I said are hydrophobic amino
acids
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After it gets
through, the signal sequence that is imbedded in the ER membrane, then translation will continue
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This event is caused by signal peptidase
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So you have
the insertion of the signal sequence in the membrane and signal peptidase cuts it off and the protein is
allowed to move into the lumen of the ER and the last event deals with chaperon proteins
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So where is the energy coming from? If this is a membrane and a newly form peptide, there is a
protein called BIP
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As the nascent
protein continues to come out another BIP will bind to it and as more protein come out more BIP will
attach to it
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Now this BIP is very interesting
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So this protein cycles until the whole peptide gets pulled inside the ER lumen
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It also has another function, after the pulling sequence
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Its not folded yet, some of the proteins can fold without any help
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Some of
them need help
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You can look at these steps as a series of chemical reactions
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I will go through the whole things again
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The first thing
that is translated is the signal sequence (which is 6-8 hydrophobic amino acids)
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This SRP will bind to it and
will complex to it
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It will bind to it
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This channel will be continuous with the channel of the ribosome where
translation is going on
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So
when the signal peptide goes through it will first be imbedded that is why it is hydrophobic
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The nascent peptide will continue to grow inside the lumen
of the ER
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After the whole peptide is finished then you have the
folding of the protein to its most stable form
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The signal sequence is very important unless it binds to the translocator, the channel will not form
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But it is the binding that will open up a channel inside the translocator protein
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I will go over it by powerpoint now
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The ribosome will not come to the ER
membrane unless there is an SRP present in the cytosol
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Only when
the signal sequence is completed you have a SRP that will bind to the signal sequence and will bend
around the ribosome
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So when it binds it
stops the translation of the protein by the ribosome
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Now you have a SRP

receptor that specifically recognizes SRP when it is bound to the ribosomal complex
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There is a protein
called translocator protein that when the signal sequence gets close enough will be triggered by the
signal and will open
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So there are 7 specific spots on the translocator protein where the
ribosomal complex will bind to, so you have this anchoring mechanism at specific points
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The signal sequence will imbedded in the ER membrane and signal peptidase will
cleave the signal
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It takes ATP hydrolysis to have the ATP leave the
peptide and then it will go and recycle back through the whole process

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