Ch 13 Pt 2 Flashcards
Lysosomes
Membrane-enclosed organelles filled with soluble hydrolytic enzymes that digest macromolecules
are more acidic than cytosol (because allows for optimal faction of acid hydrolases)
sugar modified protines on the membrane in the lysosome
are a barrier to precent digestion of protines
What happens of hydrolases leak out of the lysosome?
They will not be as active because of the pH difference.
Is a protection mechanism
Lysosome Maturation
Late endosomes - chop up and (begin) digest debree (contain material from PM and new hydrolases)-> endolysosome mature into lysosomes once hydrolases complete digestion
Delivery to lysosome
- Nutrients - receptor mediated - endocytosis
- Captures fluids
- Engulf microbe, phagocytosis
- autophagy - not begin at cell surface, begins at cytosol
Autophagy
Important in ___
can digest ___
Self Eating
Important in growth and development (helps restructure differentiating cells)
gets rid of organelles not functioning well
Can digest large objects (proteasome can’t handle)
Selective vs Nonselective Autophagy
Selective - initiated by signal - induce fusing of vesicles (capture cytosol and organelles) - forms a autophagosome - fuse with lysosome - degradation
Non selective - new born babies and in starvation conditions. Capture whatever it can be used for nutrients
How are lysosomal hydrolases recognized and selected in the Trans Golgi?
Unique Marker: Mannose-6-phosphate (M6P) - becomes tag - recognized by M6P receptor
(N linked oligosaccharide - added in ER)
Transport of lysosomal hydrolase to endosome
Happens in Golgi.
With Tag - recognize for packing into clathrin coated vesicles - sent to the lysosome
Fuse with early endosome - disassociates (receptor and protein) promoted by lower pH - release hydrolase.
Receptor is brought back with retromer coat.
I-cell disease
Inclusion-cell disease
mutation in enzyme responsible for adding M6P tag. (defect in GlcNAc phosphotransferase)
Almost all hydrolytic enzymes are missing from lysosomes of many cell types. Undigested material accumulates in lysosomes, formation of large inclusions in cells.
Hydrolases are secreted (found in blood)
organ falure (6-7 years lifespan)
Endocytosis
-cells take up PM components, fluid, solutes, macromolecules
Material ingested is enclosed by small portion of PM, which first invaginates and then pinches off, forming an endocytic vesicle
Cell regulates its membrane composition in response to changing extracellular conditions
From the Plasma Membrane to Lysosome
Most endocytic vesicles fuse with receiving compartment (early endosome), where internalized cargo is sorted.
Some returned to PM (recycling endosome) and some designated for degradation (late endosome).
Early vs late endosome
Early:
- Has tublar domains, can recycle
- Recieves endocytoic vesicles
- Vacular domain
- Branches - lost in Late
- from golgi to early - inactive enzymes (because still recycling)
- closer to plasma membrane
Late:
- more intraluminal vesicles
- no more recyling
- inc. digestion
- destin for degredation
- more actic, (enzymes that degrade are more active)
Golgi and early endosome
gets inactive enzymes (hydrolases) from golgi (zymogens)
in multivescular body
change in rabs and snares so that late can fuse with lysosome
invagenate - bring into (membrane protein) endosome for digestion
Why respond to insulin so fast
recycling endosome
strage ceter for glucose transporters, moblization to PM, uptake of glucose
Pathways of protein sorting in trans Golgi network
- gets hydrolases to lysosome (M6P R)
3.. defult pathway - make changes - bring in components un unrgulated way - gets enxymes without a tage - to PM - Regulated - singal relase of secretoy proteins (ex. NT)
Secretory proteins become highly concentrated in secretory vesicles because
Clathrin coated vesicles retrieve membrane and luminal content back to Golgi
Secretory proteins aggregate in acidic environment
Vesicles fuse
Synaptic vesicles (specialized secretory vesicles)
Docking of vesicle at presynaptic plasma membrane
Priming step: SNAREs partly paired, helices not fully wound. Complexins frexe snare complex, prevents fustion ot membrane so when singal comes it is ready
Fustion: Action potential arrives at nerve terminal, influx of Calcium ions through voltage-gated Ca2+ channels
Rise in calcium: triggers binding of Synaptotagmin (contains calcium binding domains) to phospholipids and SNAREs, displacing complexins.
Fusion pore opens and neurotransmitters are released
The botulinum toxin causes
muscle paralysis
prevents the release of acetylcholine from presynaptic axon of motor neurons.
has heavy and light chain
heacy chanin txin binds to R to be endocytosed, once in vesicle ligh chai relseased and dissables/cleaves snares so can not longer assemble
