A question from today's USMLE

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Medfarmer, although the cis-Golgi would indeed add M6P (via N-acetyl glucosaminyl-1-phosphotransferase) to proteins for trafficking to the lysosome, I would think that RER --> Golgi --> lysosome wouldn't make sense because RER proteins are all destined either for exocytosis or transmembrane-localization (via trans-Golgi). If the proteins originate from within the cell (i.e. not endocytosed), it should be free ribosome --> cis-Golgi --> lysosome, since intrinsically derived proteins are all free ribosome-translated.

Maybe my biochemistry needs some touching up, but any thoughts on that?
 
Medfarmer, although the cis-Golgi would indeed add M6P (via N-acetyl glucosaminyl-1-phosphotransferase) to proteins for trafficking to the lysosome, I would think that RER --> Golgi --> lysosome wouldn't make sense because RER proteins are all destined either for exocytosis or transmembrane-localization (via trans-Golgi). If the proteins originate from within the cell (i.e. not endocytosed), it should be free ribosome --> cis-Golgi --> lysosome, since intrinsically derived proteins are all free ribosome-translated.

Maybe my biochemistry needs some touching up, but any thoughts on that?

I believe the RER actually synthesizes any protein/enzyme that is either destined to be extracellular OR contained and retained in a membrane bound structure (such as the lysosome). It is usually referred to as "extracellular" because it has to pass through a bilipid membrane to get into the lysosome. Free ribosomes make proteins that are initially retained in the cytoplasm or non-membrane bound compartments. (this is coming from faint memories of undergrad cell bio so take it for what it is)
 
I am just going off from from high school biology, but I thought free ribosomes are for cytoplasm proteins and then the golgi apparatus just has two sides that communicate with the RER thats why its so close to the golgi.

RER --> cis-golgi --> trans-golgi --> protein modification (like 6-mannose-P if it wants to go to the lysosome) -> endosome --> lysosome

depending on the protein the trans golgi can say if it wants to excrete the protein or store it in a lysosome. if it wants to store it, it places a 6-mannose-phosphate, if not it will be excreted in a transport vesicle, or placed in the plasma membrane.

the free proteins just goes straight in the cytoplasm

Again this was my basic understanding and i could be wrong.
 
I believe the RER actually synthesizes any protein/enzyme that is either destined to be extracellular OR contained and retained in a membrane bound structure (such as the lysosome). It is usually referred to as "extracellular" because it has to pass through a bilipid membrane to get into the lysosome. Free ribosomes make proteins that are initially retained in the cytoplasm or non-membrane bound compartments. (this is coming from faint memories of undergrad cell bio so take it for what it is)

Do you believe or do you know?

Regardless as to the surface characteristics of the lysosome, it's an organelle, and free ribosomes synthesize organellar proteins.

Btw, I said in my above post that cis-Golgi --> lysosome. It should say trans-.
 
If this was an exam and it was between RER and free Ribosomes, I would click RER and I would be pretty confident it is a better answer than free ribosomes.
 
I have annotated in my FA (from Gd knows where):

"Cis-Golgi is responsible for targeting substrates to the lysosome, and it is implicated in I-cell disease. Trans-Golgi products are exocytosed."

Meanwhile, FA says cis-Golgi is for receiving proteins from the RER and trans-Golgi is for both lysosomal trafficking and exocytosis.

My question would now be if free ribosome-translated proteins are sent to the cis-Golgi. If they are, then that would make sense for I-cell disease. If they are not, then RER would have to be the source of lysosome proteins. I would assume intracellular proteins are epigenetically modified at the Golgi, making free ribosomes a reasonable source for proteins derived in I-cell disease.

Are you catching my drift?
 
I think you are a little confused. Think of cis and trans as bottom and top respectively not enter and exit (since there is anterograde and retrograde pathways).

first golgi usually works with RER since they are in close proximity to each other while you can have ribosome floating around.

second there are two pathways for the golgi, pathway A and pathway B

Pathway A (anterograde): mRNA --> RER --> proteins --> cis-Golgi --> trans-Golgi --> leave golgi (can be sent to the plasma membrane, lysosome, or excreted out)

Pathway B (retrograde): endosomes --> trans-golgi (can go to ER then back) --> lysosomes or where-ever

On page 79 of FA, 2012 it even says free ribosomes are mainly for cytocytic protein.
 
Phloston,

RER synthesizes proteins destined for lysosomes (as well as transmembrane proteins and those destined to be exocytosed).

Free ribosomes synthesize proteins destined for peroxisomes, not lysosomes.

I had a very specific question on this in Kaplan Qbank and made sure to annotate accordingly.
 
I think you are a little confused. Think of cis and trans as bottom and top respectively not enter and exit (since there is anterograde and retrograde pathways).

first golgi usually works with RER since they are in close proximity to each other while you can have ribosome floating around.

second there are two pathways for the golgi, pathway A and pathway B

Pathway A (anterograde): mRNA --> RER --> proteins --> cis-Golgi --> trans-Golgi --> leave golgi (can be sent to the plasma membrane, lysosome, or excreted out)

Pathway B (retrograde): endosomes --> trans-golgi (can go to ER then back) --> lysosomes or where-ever

On page 79 of FA, 2012 it even says free ribosomes are mainly for cytocytic protein.

P. 79 of FA doesn't say "mainly for cytocytic protein." It says "cytosolic and organellar" protein.

That also still doesn't address whether free ribosomes send their proteins to the Golgi for epigenetic modification. If they do, cis-Golgi would still be presumptive for receiving those proteins.

Phloston,

RER synthesizes proteins destined for lysosomes (as well as transmembrane proteins and those destined to be exocytosed).

Free ribosomes synthesize proteins destined for peroxisomes, not lysosomes.

I had a very specific question on this in Kaplan Qbank and made sure to annotate accordingly.

Interesting. Thanks for posting that.
 
I believe the RER actually synthesizes any protein/enzyme that is either destined to be extracellular OR contained and retained in a membrane bound structure (such as the lysosome). It is usually referred to as "extracellular" because it has to pass through a bilipid membrane to get into the lysosome. Free ribosomes make proteins that are initially retained in the cytoplasm or non-membrane bound compartments. (this is coming from faint memories of undergrad cell bio so take it for what it is)

/thread 😛

Like ctusfinest points out, RER makes proteins that are either secreted from the cell, inserted into a membrane or packed into a membrane bound vesicle. The exception to this is some peroxisomal and mitochondrial proteins which are made by free ribosomes and trafficked there by localization sequences.

If you can remember that ribosomes are found on the cytosolic side of the ER and synthesize proteins into the ER, it can help you remember where RER proteins will end up. They (the proteins) cross a membrane and enter a kind of "virtual extracellular space", ergo will end up "outside the cell" (note here I'm denoting virtual extracellular space to mean; not cytoplasm).


P. 79 of FA doesn't say "mainly for cytocytic protein." It says "cytosolic and organellar" protein.

That also still doesn't address whether free ribosomes send their proteins to the Golgi for epigenetic modification. If they do, cis-Golgi would still be presumptive for receiving those proteins.



Interesting. Thanks for posting that.


Epigenetics is the modification of DNA into active and inactive states, meaning heritable changes in gene expression. It happens in the nucleus.

The whole point (from the cell's standpoint) of all this ER and golgi business mostly has to do with getting proteins folded correctly. Modifications to the protein happen in the ER and golgi, but most important of all they provide environments suitable to protein folding.

Proteins made on free ribosomes are destined to do their work in the cytosol, so should fold correctly under cytosolic conditions. When aid is required there are cytosolic chaperone proteins that aid in folding. The cell also has cytosolic enzymes capable of post-translational modifications that work in the cytoplasm too. For example, addition of vitamin cofactors.
 
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