Intro To The Endoplasmic Reticulum Flashcards
What is the ER
A system of membranes and vesicles that forms the ER and encloses the ER lumen
The lumen is separated from the cytosol
It’s divided into the rough and smooth ER
What is the RER
Has ribosomes bound on the cytosolic membrane side of the er (outside organelle)
It’s made of a network of cisternae and it’s connected and stems from the outer membrane of the nuclear (nucleuses) envelope
What is the SER
No ribosomes
Made of interconnected curved tube like membranes
Stems from (continued from) the rough ER
What is the function of the rough ER
Role in protien synthesis and addition of surfaces to protiens
The RER is more present in Cells that have role in protien secretion
What is the function of the smooth ER
Make steroid hormones and membrane lipids, Detox organic compounds in the liver
Concentrates calcium ion in skeletal and cardiac muscles (playing a role in muscle contraction)
It’s more present in cell types of skeletal muscles, kidney tubules and steroid producing endocrine glands
What are examples of the RER in use
Acinar cells in the pancreas that secrete hydrolytic enzymes
Intestinal cells that secrete mucoprotiens
Endocrine cells that secrete polypeptide (amino acid based) hormones
What are the two types of ribosomes
RER
FREE
what are RER ribosomes
Make 1/3 of protiens
The protiens made are secreted protiens, integral membrane protiens and soluble protiens that are in parts of the Endomembrane system (in golgi, lysosomes, etc.)
They implement cotranslational translocation where peptides of the protien move into the lumen of the ER while the ribosome on the ER is making them
What are free ribosomes
What do they make
The make 2/3 of protiens
Not attached to ER, the protiens made from the ribosomes are released to the cytosol and are directed to go else where if needed
They make:
Protiens that stay in the cytosol
Peripheral (weakly bound) protiens on the cytosolic side of membranes
Proteins that are moved to the nucleus, mitochondria and chloroplasts
The FREE and RER ribosomes are ____
Structurally and functionally identical
Where does all protiens synthesis begin
What else is synthesized first
On a free ribosome (not at the ER)
A signal sequence at the N terminal end of the peptide gets synthesized first, it’s made of 6-15 hydrophobic amino acids
What is step 1 in co trans location for secreted protien and soluble protien in the Endomembrane system
A free floating signal recognition particle (SRP) binds to the signal sequence of the peptide and to the ribosome making the peptide
This stops the poly peptides synthesis temporarily
What is step 2 in co trans location for secreted protien and soluble protien in the Endomembrane system
The SRP directs the ribosome/peptide complex to the ER by binding to a SRP receptor on the ER membrane
What is step 3 in co trans location for secreted protien and soluble protien in the Endomembrane system
The SRP on the receptor tranferrse the ribosome/peptide complex to the translocon (protien pore) in the ER membrane
The SRP leaves
The plug inside the translocon reacts with the hydrophobic signal sequence on the peptide and gets displaced (opening up the pore)
What is step 4 in co trans location for secreted protien and soluble protien in the Endomembrane system
The polypeptide continues to be synthesized and enters the ER lumen (inside of Er)
after translation is terminated The ribosome is released from the membrane and synthesizes elsewhere
What happens to the protien after the ribosome is done translating the peptide in cotranslocation
Signal peptidase removes the signal sequence from the peptide
Protein chaperone BiP helps fold the protien properly
What is the first step of cotranlosacton for the synthesis of integral membrane protiens
The protien is made and in the ER the same way as before
But the SRP recognizes the 20AA LONG transmembrane domain of the protien as the signal sequence and brings that to the ER
The polypeptide passes through the translocon pore but not fully, it inserts itself into translocon pore and decides where to go from there
For translocation of integral membrane protiens how does the protien decide where to go once in the translocon
The protiens can decide to move itself out of the pore and into the ER membrane using the gates at the side of the pore
If it’s hydrophobic enough to to partition into the lipid membrane, the protien will laterally exit the pore
If not it’s will stay in the pore
For translocation of integral membrane protiens how does the protien exit the pore and orient into the ER bilayer
The direction that the peptide (N or C) is inserted depends on the placement of the positively charged amino acids
The region of the protien that will be flanking (sticking into) the cytosolic end will be the region with the positively charged amino acids POSTIVE END IN CYTOSOL
Since PS and PI phospholipids have negatively charged head groups, they would be facing the lumen NEGATIVE END IN LUMEN
what amino acids are positively charged
Arg
Lys
His
What do majority of the protiens made at the RER undergo
Glycosylation (sugars are added to them)
They turn into glycoproteins
What role do carbohydrates play in Glycosylation
They play a role as binding sites and help in proper folding/stability of the protien
They sort and direct protiens to diff cellular components
What is Nlinked Glycosylation
Common type of Glycosylation
A sugar linkage to asparagine (which is part of the larger protien) that is initiated in the RER
What is O linked Glycosylation
The sugars links to a serine or threonine in the larger peptide.
This happens in the golgi complex
What is the first step to Nlinked Glycosylation
Seven sugars are first transferred one at a time to lipid molecule in the ER membrane called dolichol pyrophosphate
The assembly of the sugars are on the cytosolic side (outside the ER)
The sugars are added by glycosyltranferases in the ER membrane
What is the second step to Nlinked Glycosylation
Dolichol pyrophosphate with its now attached oligosaccharide (7 sugars) is flipped across the membrane
Now the sugars are in the lumen of the RER
Remaining sugars and 3 glucose from the cytosolic region add to dolichol and dolichol flips and these get added onto the growing chain inside the lumen
What is the third step to Nlinked Glycosylation
The completed oligosaccharide in the lumen is transferred over to an ASPARAGINE (asn) residue of the polypeptide that’s being translated and undergoing cotanslocation
In the third step of n linked Glycosylation, how does the sugars get transferred to the peptide
It gets transferred by the enzyme oligosaccharyltransferase to an asn with this sequence:
Asn-x- ser/thr
ASN can be in middle or start of peptide
X is any AA expect proline since it causes kinks and won’t be recognized by enzymes
What are the first and second steps of quality control for misfolded proteins during co translocation
- This sugars are already on it, so glucosidase 1 and 2 remove two glucoses from the protien, leaving only one
- The remaining glycoprotein with 1 glucose is recognized by Calnexin (a chaperone protien inside the ER that helps protiens fold properly
What are the third and fourth and fitfth steps of quality control for misfolded proteins during co translocation
- Calnexin removes the last glucose from the glycoprotein , if correctly folded the protien exits the membrane
- If still misfolded, protiens are recognized by UGGT (conformation sensing enzyme) which detects exposed hydrophobic residues (show of improperly folded) and adds a glucose molecule
- Calnexin process happens again and tries to refold the protien
What are steps 6-8 of quality control for misfolded proteins during co translocation
- If properly folded the protiens exit
7-8. If still not properly folded after many attempts the protiens are degraded through a proteosome in the cytosol
