Metabolism 7 Flashcards
What are the 3 types of intracellular transport?
- Gated transport (e.g. nuclear)
- Trans-membrane transport (e.g. import of newly synthesised proteins into ER)
- Vesicular transport (inter-organellar transport)
Describe vesicular transport.
Exocytosis:
ER -> Cis -> Medial -> Trans -> Cell surface via various secretory vesicles
Endocytosis:
Pathway 1 = early endosome (involved in recycling), material can keep recirculating back to plasma membrane
- it could go to the late endosome.
- if material is destined for destruction it will be taken to the lysosome
Which golgi section is closest to ER?
cis
Where does post translational modification occur?
Golgi
Where do the ribosomes come from, that synthesise proteins that stay in the cytosol and also those that are transported into the ER?
Common Pool
At the end of each round of synthesis, ribosomal subunits are released and rejoin the common pool
What are some post translational modifications that are made?
- Folding
- Disulphide bond formation
- Glycosylation
- Proteolytic cleavages
- Assembling multimeric proteins
What happens if something goes wrong in modification?
Unassembled/misfolded proteins are retained and they are exported back into the cytosol where they are degraded.
What is CFTR?
ABC transporter-class Cl channel in epithelial cell membranes.
Most common mutation is delta f508, which causes deletion of 3 nucleotides and loss of phenylalanine.
Where are proteins sorted into vesicles?
Trans golgi network
What are the functions of golgi?
- Folding
- Protection
- Receptors
- Recognition
What 3 signals do proteins have to ensure they get to the correct compartment?
- Targeting/sorting signals
- Retention signals
- Retrieval signals
What are the 2 pathways for proteins to leave the cell?
- Constitutive pathway
2. Regulated secretory
Describe how lysosomal enzymes are sorted at the golgi network.
- Proteins destined to become lysosomes recognised in cis golgi network.
- Lysosomal hydrolase precursors are recognised in the cis golgi network.
- Carbohydrates on Lysosomal hydrolase precursor are modified by addition of a phosphate to the carb, acting as a TAG.
- Mannose phosphorylation occurs, catalysed by phosphotransferase.
- Lysosomal enzymes now tagged with a phosphorylated sugar.
- They now go to trans golf network, where the phosphorylated sugar is detected by Mannose-6-Receptor. Enzymes consequently packaged into very specific vesicles.
- Vesicles have targeting signals which are lysosome specific. Vesicles first go to late endosome.
- Late endosome has a proton pump, which pumps cytoplasmic protons into the late endosome. This gives the late endosome lumen acidic pH.
- Acidic environment causes M6P to release phosphorylated lysosomal hydrolyses.
- After release, phosphate removed (via phosphohydrolase). THIS MEANS THE LYSOSOME CANNOT GO BACK TO GOLGI AS ITS LOST ITS PHOSPHATE.
- This causes accumulation of lysosomal hydrolyses in late endosome.
- Late endosome matures to form a lysosome.
- M6P receptors recycled back to trans golgi network.
What are the 3 types of endocytosis.
- Receptor mediated endocytosis - substances bind to specific receptors, forming vesicles that have a protein coat around them
- Pinocytosis - fluid drinking. Cell extends its membrane and takes in some extracellular fluid
- Macropinocytosis/Phagocytosis - can take up large particles, e.g. bacteria
What can happen to early endosomic material (the sorting compartment)?
- Recycling - material sent back to plasma membrane
- Degradation
- Transcytosis - material carried to basolateral membrane, where it is moved across epithelial monolayer.