The Endoplasmic Reticulum Flashcards
What is the structure of the ER like?
A single-membrane compartment
A continuous network of tubular and flat vesicular structures in the cytoplasm
The space inside is connected, with the space between two membrane surfaces of the nuclear membrane- continuous with the nuclear envelope
What are the two types and functions of the ER?
Granular/rough ER- ribosomes attached for the translation and folding of new proteins
Found nearer to the nucleus
Agranular/smooth ER- synthesis of lipids and detoxification of certain drugs and toxin by cytochrome P450 enzymes
Found closer to the membrane
What processes is each of the ER involved in?
RER- protein synthesis, glycosylation, folding and assembly and multi-proteins complexes
SER- lipid synthesis (cholesterol, phospholipids)
Ca2+ sequestration- regulates the concentration of calcium
Detoxification by cytochrome P450 enzymes
What is a signal sequence and what does it do?
Signal sequences are amino acids at the N-terminal end of the protein that are recognised by enzyme systems within the cell that transport the protein to the correct destination
Newly synthesised proteins are targeted to ER, nucleus, mitochondria or peroxisomes
This is done through signal sequences
Recall the steps of the SRP cycle (for the synthesis, translocation and transport of proteins to the RER)?
- The recognition of the signal peptide (at the N-terminal) by the ribosome
- The SRP protein binds the ribosome nascent chain complex- a growing complex formed by the ribosome and the amino acid chain
- This bound complex binds to the SRP receptor, GTP needs to be present in order to establish it
- The signal peptide is then transferred from the SRP complex to the translocation channel (TLC)
- The SRP complex (SRP, SR receptor, the ribosome and the nascent chain) is going to translocate and move around until it finds a TLC on the endoplasmic reticulum
- Then GTP hydrolysis happens and the complex is dissociated
- The protein will already be placed inside the translocation channel with the ribosome
- The SRP can be recycled
What is the Signal Recognition Particle (SRP)?
The signal recognition particle is a ribonuclear protein, a complex of protein and RNA, that is very abundant in the cytoplasm of all cells
The SRP will recognise and target a specific protein to the endoplasmic reticulum
What happens to proteins in the RER? What happens to insulin specifically?
Proteins are modified
Insulin modifications start in the RER and finish in the Golgi apparatus
Insulin is initially synthesised as preproinsulin
The first step is proteolysis- removal of the signal peptide
Then the proinsulin is cleaved into three different peptides- A, B and C
Then you get the formation of disulphide bonds between A and B and removal of C
The mature insulin needs to be glycosylated and deglycosylated
The proteins are the folded to tertiary and quaternary shape and directed to Golgi or elsewhere
Why is glycosylation important for secreted proteins?
The phosphorylation of mannose so that these proteins that are going to be secreted are already target in this process by the phosphorylation of one of their mannose sugars creating a recognition signal so that the protein is directed to the lysosomes
What happens proteins that fail a quality check?
Proteins that fail will not be exported from the ER and are degraded by ubiquitination and proteasome
ERAD- Endoplasmic-reticulum-associated protein degradation
What is the structure of the Golgi apparatus like?
A single membrane compartment consisting of 4 to 8 stacked layers of thin, flat, enclosed vesicles, cisternae, lying near one side of the nucleus
What are the three networks that make up the Golgi apparatus?
Cis- first cisternae structure, closer to the nucleus
Medial and trans compartments- final structure, closer to the cell membrane
What is the function of the Golgi apparatus (with examples)?
Protein modification for: Glycosidases, glycotransferases O-linked glycosylation Sulfatases Proteases Lipid synthesis for: Sphingomyelin GLucosylceramide Protein and lipid sorting to: Secretory granules Plasma membrane Basolateral versus apical membrane Endosomes Lysosomes
How does cargo get transported around the Golgi apparatus?
Vesicles fuse to the Golgi and deposit their cargo inside the complex
Stages:
Budding
Movement
Fusion
Vesicles transport proteins form one cisternae to another
What are the pathways vesicles can transport proteins?
From the Golgi apparatus to lysosomes, the plasma membrane or the exterior
From the plasma membrane to lysosomes
From the endosomes to the plasma membrane
What happens to vesicles when they transport proteins?
Destination is determined in the ER when the protein/cargo bond to specific receptor
Various characteristics of the cargo protein are recognised (e.g. aa sequence or added CHO)
Bud formation is facilitated by binding of different Coat proteins (e.g. COPs)
Once transport vesicle is formed and released, COat proteins are removed by revealing v-SNARE (integral protein)
v-SNARE binds to t-SNARE (target) in the target membrane, the transport vesicle fuses to the target membrane and the cargo is delivered
