Lecture 23 - Extracellular vesicles and the inflammation pathway Flashcards
What are microvesicles?
They are vesicles that bud off the plasma membrane into the ECM, mostly constant size.
Where are exosomes derived from?
Derived from early endosomes, they are vesicles within them, forming a multivesicular endosome.
Most end up as lysosomes. Others may merge with the plasma membrane to release their exosomes, which are irregularly shaped.
What are the function of extracellular vesicles?
Regulate immunity Transfer antigens Suppress immune response to tumours Suppress immune response to self-antigens Transduce signals in cancer
What are the characteristics of extracellular vesicles?
They are enriched for: certain proteins (tsg101) endosomal proteins (GPIs & flotillin) microdomain proteins (tetraspanins) certain lipids and cholesterols specific RNAs
They contain both mRNA and miRNA
What are the mechanisms exosomes?
Transcellular transfer of mRNA (protein expression), miRNA (gene expression inhibition) and proteins (hormones, transcription factors etc)
How can some diseases be detected early via exosomal activity?
Some diseases can be detected from the blood before symptoms manifest due to the action of exosomes with characteristic markers being present in the blood.
What is the main mechanism of HIV inection?
It begins with a CD41 cell infection, which is detected and taken up by a dendritic cell.
The dendritic cell expresses it to present to more CD41 cells, transfecting them too.
What is the mechanism of prion infection?
Exosomes containing the prions are secreted, especially distant to the site of infection.
Allows early diagnosis by exosomal analysis.
What are esRNA and what is their function believed to be?
They are RNA found in extracellular vesicles and exosomes.
They are believed to be involved in cell signalling via protein expression (mRNA) or inhibition (miRNA)
Do tumours release exosomes? Why is this important in diagnosis?
Yes, they release exosomes (with esRNA in them). Different tumours have different miRNA profiles.
Allows profiling of the cancer from bodily fluids, via the esRNA.
What are JAKs, and what are they involved in?
JAKs are receptor linked kinases involved in cell surface signalling and phosphorylate STATs, activating the inflammation pathway.
What is the function of SOCS?
It inhibits the JAK/STAT pathway, regulating inflammation.
How is IL-6 associated with inflammation?
It is associated with a JAK that phosphorylates STAT3.
How is inflammation inhibited?
It was found that aveolar culture of mice (and men) suppressed STAT phosphorylation.
The mediator was found to be SOCS.
Describe how SOCS was found to inhibit inflammation.
First, SOCS3 translation is inhibited by interference RNA (siRNA) specific to SOCS3 in aveolar culture (of mice). Does so by breaking down the mRNA responsible for SOCS3 translation.
When combined with epithelial cells, the suppressing ability was negated, suggesting SOCS prevents phosphorylation.
