Lecture 18 - Intracellular Vesicular Transport II Flashcards
What is a lysosome?
- compartment containing hydrolytic enzymes
- intracellular digestion of macromolecules
- acidic internal environment pH ~5
- vacuolar ATPase maintains pH
- derived from late endosome
What pathways lead to the lysosome?
- phagocytosis
- endocytosis
- autophagy
What is autophagy?
- damaged organelles are surrounded by a membrane and are isolated creating an autophagosome
- autophagosome fuses with lysosome and damaged organelle is degraded
How are lysosomal proteins formed and transported to the lysosome?
- co-translationally transported into RER
- transported to TGN via Golgi, while in Golgi mannose-6-phosphate (M6P) is attached to the protein as a sorting signal by GlcNAc phosphotransferase
- M6P receptors bind M6P and facilitate formation of clathrin coated vesicles
- vesicle merges with endosome
- endosome fuses with lysosome
What is GlcNAc phosphotransferase?
-protein responsible for phosphorylating mannose to make the signaling sequence for lysosomal proteins
Hurlers disease and inclusion cell disease
- Hurlers Disease-Mutation in the enzyme required to break down GAG chains.
- Inclusion cell disease-ALL of the lysomal hydrolases are missing in many cell types. Undigested substrates accumulate as inclusions.
What is endocytosis?
- uptake of macromolecules from exteriors
- invagination of cell membrane to form a vesicle
What are the different types of endocytosis?
Pinocytosis:
- small particles
- pinocytic vesicles
Phagocytosis:
- large particles
- phagosomes
What is receptor-mediated endocytosis?
- import of select molecules though endocytosis
- achieved using receptors for specific substance in clathrin coated pits
Used in cholesterol uptake
What are the possible outcomes for a endocytosis receptor protein?
Degradation
Recycling
-return to original membrane region by recycling transport vesicle
Transcytosis
-insertion in opposition site of cell membrane
What is the mechanism through which phagocytosis occurs?
- antibodies or other substances target a body to be phagocytized
- receptors on macrophage/neutrophil trigger formation of pseudopodium by actin fiber rearrangement when bound
- pseudopods envelop target body and form a phagosome
- phagosome is directed to lysosome by phosphoinositide signaling
What are the two processes by which pinocytosis occurs?
Clathrin coated pits:
-membrane invaginates and pinches off
Caveolae:
- caveolae; flask shaped invaginations caused by high presence of cholesterol and glycosphingolipids
- structural protein is caveolin
- pinch of with dynamin
- from caveosome which does not fuse with lysosome
What is exocytosis?
- movement of transport vesicles from TGN to cell membrane
- membrane proteins in vesicle incorporate into cell membrane
- soluble proteins are secreted
What are the two types of exocytosis?
Constitutive:
-occurs continuously
Regulated:
-signal causes fusion of transport vesicle and is required for exocytosis