Metabolism 7- Membrane trafficking Flashcards
What are the different sections of the Golgi apparatus
The Golgi Apparatus has three sections: cis, medial and trans
The cis Golgi network is closest to the ER.
When is Exocytosis uses in the cell
Endoplasmic Reticulum –> Cis Golgi network
Cis Golgi Network –> Medial Golgi Apparatus –> Trans Golgi Network
Trans Golgi Network –> Cell Surface via different types of secretory vesicle
Types of Intracellular Transport
Gated Transport - e.g. nuclear import
Trans-membrane Transport - e.g. import of newly synthesised proteins into ER
Vesicular Transport - e.g. inter-organellar transport
Endocytosis Overview:
Material recognised at plasma membrane is brought in via endocytic pathway
First pathway is the Early Endosome (involved in recycling) - material from early endosome can recycle back to the plasma membrane and keep going round and round.
Or it can be sorted into another compartment called the Late Endosome.
If the material is destined for destruction it will be taken to the lysosome to be broken down.
Describe the Secretory or Exocytic Pathway
Overall movement is from the rER, through the Golgi apparatus and to the plasma membrane.
The membrane bound polyribosomes make the proteins.
The proteins are incorporated into vesicles which bud off and then are transported to the Cis Golgi Apparatus.
Proteins then pass through the Golgi apparatus and undergoes post-translational modification.
The proteins then eventually reach the far side of the Golgi apparatus called the Trans Golgi Apparatus.
Here the proteins are sorted into specific transport vesicles which then go to different destinations.
Transport through the Secretory Pathway
SRP (signal-recognition particle) which has to bind with an SRP receptor on ER membrane before translation continues
A common pool of ribosomes is used to synthesise both the proteins that stay in the cytosol and those that are transported into the ER (secreted and transmembrane).
The ER signal peptide on a newly formed polypeptide directs the engaged ribosome to the ER membrane.
At the end of each round of protein synthesis, the ribosomal subunits are released and rejoin the common pool in the cytosol.
Move post translations modifications can occur?
Folding
Formation of disulphide bonds
Glycosylation (addition of sugars)
Specific proteolytic cleavages
Assembly of multimeric proteins
What happens to the protein after its been modified?
The protein will move via vesicles which bud off the ER to the next stage of exocytosis.
If something goes wrong in the modification - unassembled and misfolded proteins are retained in the ER and exported back into the cytosol where they are degraded.
What is Cystic Fibrosis Transmembrane-Conductance Regulator (CFTR)
CFTR is an ABC transporter-class chloride channel in epithelial cell plasma membranes.
Mutations of the CFTR gene affects the functioning of the chloride channels in the membrane which causes Cystic Fibrosis.
How is cystic fibrosis caused
The most common mutation (ΔF508) results from DELETION of three nucleotides which causes the loss of phenylalanine (Phe) at the 508th position on the protein.
As a result, the CFTR does not fold properly and is degraded in the ER.
What signals are associated with proteins making sure they are in the right compartment
Targeting/Sorting signals (e.g. lysosomes)
Retention signals
Retrieval signals
What is the Constitutive Secretory Pathway
in all cells protiens continually going out towards the plasma membrane in an unregulated manner.
What it the Regulated Secretory Pathway
for materials which have to be secreted in a regulated manner e.g. neurotransmitter. Proteins, such as neurotransmitter, will be sorted into a specific secretory vesicle and the vesicle is stored in the cytoplasm until its release is triggered by a SIGNAL e.g. hormone.
How are stored secretory proteins released?
signal molecule (e.g. hormone) binds to the cell surface receptor it triggers an intracellular signalling pathways which causes the release of the stored secretory proteins.
Describe the Sorting at the Trans-Golgi Network of Lysosomal Enzymes
Lysosomal hydrolase precursors are recognised in the cis Golgi network.
The carbohydrates on the Lysosomal hydrolase precursor are modified by the addition of a phosphate onto the carbohydrate which acts as a TAG.
The phosphorylation of mannose is catalysed by PHOSPHOTRANSFERASE. (using ATP as the phosphate donor)
Now the lysosomal enzymes are tagged with a phosphorylated sugar - a very specific tag.
When they reach the trans Golgi network, the phosphorylated sugar is detected by a very specific receptor - Manose-6-Phosphate receptor - which leads to the enzymes being packaged into specific vesicles.
The specific vesicles have targeting signals on the outside which are specific to the lysosome but the vesicles travel first to the late endosome.
The late endosome contains a proton pump which pumps protons from the cytoplasm into the late endosome so THE LUMEN OF THE LATE ENDOSOME IS RELATIVELY ACIDIC.
In the acidic environment the M6P receptor releases the phosphorylated lysosomal hydrolases.
Once released, the phosphate is removed by a phosphohydrolase - SO IT CAN NO LONGER GO BACK TO THE GOLGI BECAUSE IT DOES NOT HAVE IT’S PHOSPHATE.
Because of this mechanism, you get an accumulation of lysosomal hydrolases in the late endosome.
THE LATE ENDOSOME MATURES TO FORM A LYSOSOME.
The M6P receptors are recycled back to the trans Golgi network.
