Lecture 15 - the endocytic pathway Flashcards
Phagocytosis in protozoans
Uptake of large matter (>0.5microns)
Source of food
Forms a phagosome, fuses with phagolysosome where the internal matter is degraded
Phagocytosis in animals
Specialised cells - professional phagocytes etc
Ingest:
* Invading microorganisms
* Senescent cells
* Apoptotic cells
Actin-dependent process, pseudopodia engulfs bacterium after recognising the antibody that had bound using its Fc region
Endocytosis
Pinocytosis - smaller particles/liquid
Constitutive process - all cells (except RBCs) doing it constantly
- Caveolae
- Macropinosomes
- Clathrin-coated pits
Caveolae
Made of caveolin
Rich in cholesterol and GPI-anchored proteins
Pinch off to form caveolar vesicles - fuse with endosome-like compartment called caveosome
LIPID RAFTS OFTEN FORM HERE????!!!!
Macropinocytosis
Uptake of large amounts of lipid
Actin-dependent process
- PM protrusion (actin-dependent ruffling)
- Vacuole closure
- Macropinocytosis
Receptor-mediated endocytosis
Efficient uptake of specific components via cell surface receptors
Clathrin-dependent
Constitutive - LDL receptor
Induced - EGF receptor
Internalisation signal - ie NPXY in LDL receptor - mutated in some FH patients
LDL endocytosis
LDL - how we circulate cholesterol
- LDL receptor binds
- Clathrin gathers onto the receptors
- Vesicle is formed
- Moves to endosome (acidic - receptors release from LDLs, they are then recycled)
- Then move to lysosome for degradation
- Free cholesterol moved to cytoplasm
Familial hypercholesterolemia
Genetically inherited
High blood cholesterol - LDL defective uptake
- Missing in LDL receptor
- Mutations in LDL receptor binding region
- LDL mutated to have a defective coated pit binding site
Early endosome fusion
Main sorting station in endocytic pathway
Acidic environment - most receptors release cargo after undergoing a conformational change
Receptors:
* Recycled to the PM
* Transported to different domain of the PM (transcytosis)
* Transported to the lysosome
Endocytic vesicles uncoat and fuse with early endosomes - regulated by Rab5
Early endosomes may also undergo homotypic fusion - fuse with each other
Transcytosis
Polarised epithelial cells - transport from one extracellular space to another
Ie - transport of antibodies across gut epithelium in newborns
Fc receptors bind IgA at acidic pH (in the gut/endosomes) and then release it at neutral pH (extracellular fluid)
Consequences of bad internalisation and degradation
- Less receptors at cell surface
- Cells desensitised to signal (ie EGF)
- Potential issues (ie cancer formation)
Endosomal maturation
- Multivesicular bodies continue to bud inward vesicles
- Switch Rab (5-7) and phosphoinositide composition
- Lose proteins recycled to PM and gain proteins delivered from the TGN
- Accumulate vacuolar ATPase proton pumps to increase acidification of the lumen
Consequence - early-late endosome transformation
Why may signalling continue after uptake into endosomes?
The receptor is still facing the outside of the vesicle so may still be active under the right circumstances
Needs to be removed by ESCRTs
ESCRTs
Remove receptors from endosomes, inactivating them and preventing them from being constitutively activated
Defects where these are unable to do their function often result in cancers
