Signalling molecules Flashcards
1
Q
exosomes
A
- endosomal origin extracellular vesicles
- Exosomes are formed in MVEs (multivesicular endosomes)
- Exosome formation starts with the invagination of the MVE to generate intraluminal vesicles (ILVs)
- The generation of MVEs involves the lateral segregation of cargo at the delimiting membrane of an endosome and inward budding and pinching of vesicles into the endosomal lumen (highly specific protein selection)
2
Q
microvesicles
A
- Microvesicles are small, plasma membrane-derived particles that are released into the extracellular environment by the outward budding and fission of the plasma membrane.
- This budding process involves multiple signalling pathways including the elevation of intracellular calcium and reorganization of the cell’s structural scaffolding.
- The formation and release of microvesicles involve contractile machinery that draws opposing membranes together before pinching off the membrane connection and launching the vesicle into the extracellular space.
- Microvesicles budding takes place at unique locations on the cell membrane that are enriched with specific lipids and proteins reflecting their cellular origin.
3
Q
EVs binding and internalisation
A
- Target cell specificity for binding of exosomes (or other EVs) is likely to be determined by adhesion molecules, such as integrins, that are present in EVs
- After binding to recipient cells, EVs may remain stably associated with the plasma membrane or dissociate, directly fuse with the plasma membrane (microvesicles), or be internalized through distinct endocytic pathways (exosomes)
- When endocytosed, exosomes may subsequently fuse with the endosomal delimiting membrane to then be released into the cytoplasm, or be targeted to lysosomes for degradation
4
Q
protein secretion routes
A
- proteins that have entered the ER and are destined for the Golgi apparatus or beyond are first selectively packaged into small COPII-coated transport vesicles.
- Proteins that need to leave the ER have exit signals ( poorly understood)
• They bind to cargo receptors on the ER membrane to transfer the exit signal to the cargo receptor
• This exit signal is now on the outside of the ER membrane which can be recognised by proteins part of the COPII-coat - After transport vesicles have budded from ER exit sites and have shed their coat, they begin to fuse with one another to form vesicular tubular clusters
- retrogate vesicles form coated in COP1coats to transport ER proteins back - The vesicular tubular clusters then reach the cis Golgi network and fuse to release their content into the Golgi system for sorting and modifications
- proteins leave golgi to go to: membrane, cytosol, lysosome, EVs
5
Q
synaptic signalling
A
- When an action potential arrives at the axon terminal, it activates voltage-gated calcium channels in the cell membrane.
- Calcium which is present at a much higher concentration outside the neuron than inside, rushes into the cell.
- Calcium ions allow synaptic vesicles, that contain neurotransmitters, to fuse with the axon terminal membrane, releasing neurotransmitter into the synaptic cleft.
- The neurotransmitters diffuse across the synaptic cleft and bind to receptor proteins on the postsynaptic cell.
- Activation of postsynaptic receptors leads to the opening or closing of ion channels in the cell membrane.
- This may be depolarizing—make the inside of the cell more positive—or hyperpolarizing—make the inside of the cell more negative—depending on the ions involved.
6
Q
gasotransmitters
A
- freely permeable to membranes
- enzymatically generated
- auto, para and endocrine function
- NO (nitric oxide)
- CO
- hydrogen sulfide
7
Q
nitric oxide - synthesis and function
A
- Ach binds to receptor
- IP3 is produced
- ER gates open Ca2+ is released
- Calmodulin is activated
- NOS is activated
- arginine –> citrulline + NO
- NO activated guanyly cyclase activation
- GTP –> cGMP
- PKG is activated
- muscle relaxation and vasodilation
8
Q
carbon monoxide
A
- synthesized by heme oxygenase (HO1 or 2) from heme (erythrocytes)
- has similar target as NO –> guanylate cyclase (cGMP)
- has more targets like; AKT and MAPK (anti apoptotic and anti-proliferative)
9
Q
hydrogen sulfide (H2S)
A
- synthesized from cysteine by CBS or CSE (cystathione beta synthase and ‘’ gamma lyase)
- H2S causes: angiogensis, vasodilation, lower respiration/metabolism, anti-inflammatory, Nrf2 (less ROS)
10
Q
NO, CO and H2S
A
- togetehr provide cardia and vascular protection:
- h2S –> vasodilation, anti-inflam, angiogenesis, anti-apop, NRF2
- NO –> vasodialtion, anti-inflam, angiogenesis, anti-apop
- CO –> vasodialtion, anti-inflam, angiogenesis, anti-apop
11
Q
RNA as signalling molecules
A
- RNAs can be in EVs (or lipoproteins) and serve as signalling molecules
- miRNA can serve as signalling molecules by inhibiting RNAs of different cell or by completely breaking the RNAs (less common, not specific enough in eukaryotes)
- cancer can use miRNAs to spread metastasizing phenotype
12
Q
lipid-derivatives as signalling molecules
A
- lipids do not need vesicles are often bound to transporter proteins (albumin) and can freely diffuse through membranes
- enzymatic synthesis
- eicosanoids (prostaglandins - nuclear receptor activator)
- fatty acids
- sphingolipids (G-coupled receptors)
- steroids (hormones - nuclear receptor activator)
13
Q
hormones
A
- amine hormones (adrenaline) - tyrosine
- peptide hormones (growth hormones, insulin) - prohormones
- steroids (test) - cholesterol
- eicosanoids (prostaglandins) - arachidonic acid
