Lecture 15 -Membrane trafficking in disease Flashcards
What are rab proteins and their role in cellular trafficking?
Rab proteins are a member of the Rat superfamily.
They cycle between GDP + GTP form
GDP = cytoplasm, GTP = membrane
They are required for fusion and many other trafficking functions.
It is found in the early stages of endosyti pathway.
Allows sophisticated regulation of trafficking steps
What does the Golgi do ?
It sorts out everything during vesicle transport. It distributes proteins and lipids from the ER and packages them in vesicles and passes them to the plasma membrane.
After protein is synthesised the Golgi modifies and adds oligosaccharides on the asparagine residues.
The protein will be sent to the lysosome. Endosomes will take matreil form out of cell or Golgi and will send them to either, lysosome, membrane or Golgi for more use.
What does SRP stand for ?
Signal recognition particle.
What does the SRP do ?
Will transport the protein-ribosome complex to the rough ER by docking onto SRP receptor. Allows protein translated and transported
What happens if SRP is defective or absent ?
The excess protein accumulates in cytosol
What are the 3 types of vesicular trafficking coat proteins?
COPI protein that coats the vesicle for retrograde transport. Will bring the vesicle from the cisgolgi to ER), retro because its moving towards centre of cell.
COPII. Coats vesicles for anterograde transport. Will bring the vesicle from the ER to the cis-golgi
Clathrin transports protein from trans-Golgi to lysosomes or plasma membrane to lysosome through receptor-mediated endocytosis
They form coats around membranes to force the creation of a protein. They work by binding a portion of the membrane and bud iff piece of membrane to make a vesicle
What are the 2 main types of protein trafficking?
Vesicle-mediated trafficking and non-vesicle mediated
Describe ER targeting
Mature mRNA leaves nucleus ro dinf a free floating ribosome.
Transation and protein starts forming, SRP recignises a unique a in growing polypeptide chain.
SRP brid to this aa sequence.
It binds a pore in ER membrane and brings ribsome-protein complex into ER.
The rest of the protein is synthesised in ER an protein becomes part of ER vesicular transport system.
What is endocytosis ?
Cells use this process to take in foreign material into the cell by making vesicle from the plasma membranes.
What are the 2 sides of golgi ?
Side that faces ER and the one that faces plasma membrane
Sis- golgi - ER immature proteins
Trans-golgi - membrane - mature proteins that are ready to be sent out
What is the difference between contistuitvie secretion and regulated ?
Constitutive - vesicles are constantly, undergoing exocytosis. - default pathway
Regulated - loaded vesicles are stored in cytosol until a release signal is recieved.
What does a mutations in the SEC23A gene disrupt ?
Mutations in the SEC23A gene disrupt the normal function of the protein it encodes, which is a component of the COPII protein complex. The COPII complex is responsible for packaging proteins into transport vesicles that bud off from the endoplasmic reticulum (ER) and deliver the proteins to the Golgi apparatus for further processing and sorting.
What does disrupted protein trafficking lead to other than CLSD ?
Disrupted protein trafficking can subsequently affect the activity and function of Rab proteins, as they are involved in various steps of vesicular transport.
What do Adaptor proteins do?
Recognise and select cargo ensuring specificity.
They link the coat to the membrane- > coat protein has no lipid binding proteins
Adaptors recognise motifs in the cytoplasmic domains of membrane proteins -> go to correct membrane
How do adaptor complexes show a precise sub cellular localisation ?
Need to link to the correct membrane
Proteins are specific for cargo and location.
AP1 - localised on Endosome and TGN
AP2 - Plasma membrane
AP3 - TGN, lysosomal related organelles
These proteins have similar structures and recognise similar structures and recognise similar signals
