Lysosomes Flashcards
What sort of materials get sent to the lysosomes?
Lysosome enzyme that come from the Golgi, material from the outside of the cell, organelles that are breaking down
Why do lysosomes have to constantly be created?
The enzymes inside break down everything from proteins to lipids to carbohydrates, so lysosomes will eventually eat themselves
What components of a lysosome change as it matures?
pH and enzyme composition
What is an early endosome?
The earliest stage of lysosomal maturation. They have a pH of 6.5-6.8, so the enzymes aren’t active
What is a late endosome?
When the early endosome becomes more acidic (5.5 - 4.5) and the enzymes start to work
How do endosomes get the acidic pH?
They have a proton pump and as time goes on they mature and become more acidic
Do cytosolic and nuclear proteins get degraded in lysosomes?
No. They get ubiquinated and sent to the proteosomes for degradation
What is the general name for enzymes that work in the lysosomes?
Acid hydrolases
What feature do lysosomes have that slows down the process of them eating themselves?
A thick layer of carbohydrates, but the lysosome is done for once that gets degraded
What stops the lysosomal enzymes from degrading every else in the cell when the lysosome breaks open?
The pH. The enzymes don’t work at a neutral pH, so the enzymes stop working right away
How are proteins targeted to the lysosome?
They have a sugar chain that acts as the signal sequence, instead of an amino acid sequence. That chain has a mannose-6-phosphate on it, which is the sequence. There are M6P receptors in the trans-golgi network that bind to the M6P sequence, and a vesicle going to the lysosome is formed
How is the mannose-6-phosphate signal sequence created?
The default sugar branch added to every protein going through the ER gets a phosphate stuck on the 6th position of a mannose, which stops any more modifications that would normally be done to secretory proteins
What is the enzyme that adds the phosphate to the mannose? Why is it not a kinase?
GlcNAc phosphotransferase. Kinases add phosphates to serine, threonine, and tyrosine, and this phosphate is being added to a mannose instead
What is the coat protein used for vesicles going to the lysosomes?
Clathrin
How do the lysosomal proteins dissociate from the M6P receptors? What stops them from rebinding?
The lower pH lowers their affinity for each other and causes them to dissociate. A phosphatase is waiting in the endosome and it cleaves the phosphate off the mannose, so it can’t bind to the receptor at all
Which two proteins form clathrin coated vesicles?
Clathrin forms the outer layer, and the inner layer is made of adaptin/AP2/Adapters
What is the structure of clathrin? What is the structure formed when they polymerize?
Triskelion. Each arm has a heavy chain and a light chain of clathrin. Forms a polygonal lattice when they polymerize and causes the curvature needed for the vesicle to bud off
Which G protein is responsible for the assembly of clathrin coated vesicles?
ARF
What protein is responsible for pinching off clathrin coated vesicles? What does the same thing for COPI and COPII coated vesicles?
Dynamin is used for clathrin vesicles. What COPI and COPII vesicles use is unknown
What provides the energy needed for dynamin to pinch off the vesicle?
GTP hydrolysis
