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 residues
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
Detection by chaperones: Misfolded proteins are detected by ER chaperones.
UPR activation: The UPR is triggered to restore ER homeostasis.
ERAD: Misfolded proteins are ubiquitinated and degraded by the proteasome.
ER-phagy: Autophagy selectively degrades ER portions containing misfolded proteins.
Apoptosis: If stress is unmanageable, the cell may initiate programmed cell death
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 that isessential for insertion and orienting protein in cellular membranes
How can proteins be inserted into the ER membrane
Can happen co translationally or post translationally
What is the difference between co and post translational translocation
Co-translational translocation occurs while the protein is still being translated whereas post translational translocation occurs after the polypeptide has been translated by cytosolic ribosomes
What is post translational translocation
Proteins are fully synthesized by ribosomes in the cytosol before they are translocated to their target organelles.
Targeting Signals: Proteins destined for specific organelles have targeting signals, usually short amino acid sequences, that direct them to their correct location.
Chaperones: Cytosolic chaperone proteins often assist in keeping the newly synthesized proteins in an unfolded state, which is necessary for their translocation across membranes.
Translocation Channels: The proteins pass through translocation channels or complexes in the membranes of organelles
What is a translocon
Translocons are composed of several ER membrane proteins that associate to form an aqueous pore through which secretory proteins and lumenal domains of membrane proteins pass from the cytoplasm to the ER lumen. These sites are not passive holes in the bilayer, but instead are quite dynamic
The channel is gated by a short alpha helix that is through to keep translocator closed when it isn’t being used and to move aside when a polypeptide is going through
What is the role of a translocator/translocon
What happens to water soluble proteins during translocation
They are completely translocated through the ER membrane and released into the lumen
What happens to transmembrane proteins during translocation
They become embedded in the ER membrane
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
