The Endoplasmic Reticulum Flashcards
What is the function of the endoplasmic reticulum
Function focused on proteins (and lipids)
Most membrane proteins assembled in the ER membrane
Starting point of all secreted proteins
Starting point for most proteins destined for lumen of ER, Golgi and lysosomes
Proteins are folded here and modified
Major site of quality control
Cellular lipids also made in ER membrane
What is the rough endoplasmic reticulum
Ribosomes on rER
Correlation of rER with capacity of cells to secrete proteins
Membrane-found ribosomes synthesise secretory proteins
How does a cell make a protein to be secreted
The signal hypothesis- prediction that newly synthesised proteins have a built in signal which directs them to the ER and through a channel in the membrane, onwards to their destination
Mechanism where proteins insert into or across a membrane are synthesised by membrane-bound ribosomes
Signal peptide guides positioning of the ribosome to the membrane
What are the three options for a new protein
If it has no targetting/signal sequence= released form ribosome to the cytosol (default pathway)
If it has organelle-specific targetting sequence= released then imported (e.g mitochondria, chloroplasts, peroxisomes or nucleus - NLS)
If it has an ER signal sequence = will enter ER and join the secretory pathway
What are signal peptides (or signal patches)
Sequence of amino acid that are exposed in the folded protein
Regions of aa (separated from each other in the unfolded protein) that need to be juxtaposed to function as a transport signal (harder to predict)
What are the different types of signals and their typical sequence peptide
Some proteins have more than one
Typically at the N-terminus
Where does the synthesis of all proteins begin
Begins in the cytoplasm
Signal for ER translocation is N-terminal positive , hydrophobic, polar
What is co-translation translocation
Most general mode
Utilises signal-recognition particle (SRP) and SRP receptor
Energy comes from translational (GTP hydrolysis)
SRPs move between ER membrane and cytosol binding to any ER signal sequence
That ER signal sequence= ‘start transfer sequence’
SRP binds this in a cleft (and the ribosome) and pauses translation dual recognition of signal peptide by SRP in cytosol and by translocator at ER membrane (in pore) allows selective proteins into ER
What happens during the translocation of protein into ER
After engagement with translocator:
1. Polypeptide translocates through pore in translocator
2. Signal peptide see clips off the signal peptide
3. Mature protein released into ER lumen
4. Translocator closed
What is sec translocon
Used in both co and post translational translocation
Passive pore- associating partners provide energy. Depending on partner there are different ways the channel can work
Aqueous pore
Closed by a plug when unused= gated
Polypeptide fed unfolded through cores hydrophobic lining
Core can also open along side to let cleaved signal sequence out and to integrate membrane proteins into plasma membrane
What is the sec translocon pore and plug
Helical plug blocks channel in closed state
Pore lined by hydrophobic resumes
Cross linking experiments confirm movement of the plug during translocation
What is the role of the smooth endoplasmic reticulum
- makes and metabolises fats such as those involved in steroid hormone synthesis from cholesterol
- in liver SER makes lipoprotein lipid carriers and detoxifies lipid-soluble drugs, poisons and metabolites, makes them water soluble for excretion
- SER also a major calcium ion store
Regions of SER specialised for calcium ion storage
What happens to proteins that are misfolded in the ER
They are exported from the ER
Only correctly folded and asembled proteins should leave the ER
Chaperones facilitate translocation of misfolded units out of cytosol
Degyclosylation, uniquitrination, protea some and unfolded protein response (UPR)
How are soluble proteins modified in the ER
Assembly of multi-subunit/multimeric proteins
Cleavage of some specific sites
Addition of GPE anchors
Synthesising of cell membrane lipids
There is also N-linked oligosaccharide addition that starts in the rough ER with addition of a large preformed oligosachharise precursor - N- linked glycosylation
What is meant by topogenic sequence
Collective term used for a peptide sequence essential for insertion and orienting protein in cellular membranes
What is post translational translocation
What is the role of a translocator
Describe the process of translocation through the ER membrane for water soluble proteins
N-terminal signal sequence initiates translocation
What is a stop transfer sequence
Describe how transmembrane proteins are translocated through the membrane
What is the function of the ER
What is the basic structure of the ER
