9-4 Lysosomes and Lysosomal Dz Flashcards
1)What are the Major characteristics of Lysosomes [4]
2-What makes Lysosomes different than early endosomes?
1) Eukaryotic organelle (Vacuole in plants) with enclosed degradative hydrolases, pH of 5, special membrane proteins [LAMPs] and
proton concentration 100 times > than ph7!
2)Early endosomes->Late endosomes–>Lysosomes and with EACH step the pH gets lower! [lysosomes are at the “end” of the endocytic pathway
1) How are Fibroblast involved with connective tissue remodeling?
2) Why are Lysosomes even important for remodeling and maintenance of connective tissue matrix??
3) )What is the problem with this?
1)Fibroblast/cells like-it help w/remodeling connective tissue by repairing cells with carbohydrate-rich glycocalyx, proteoglycans and glycoproteins on external surface.
**Lysosomes are the opposite end of this and work to DEGRADE MATRIX CONSTITUENTS. The balance of matrix synthesis vs. Degradation is iMPORTANT!–>prevents matrix buildup/Storage Dz
3)Lysosomes inner lining ALSO has this protective matrix-like glycocalyx to protect its own membrane from self-degradation. To fix this..Lysosomes break down these particular proteins sequentially since usually its innately protected
Extracell Matrix Proteins, Cell Surface Proteins and Membrane lipids all internalize by ___________
Extracellular Matrix Proteins, Cell Surface Proteins and Membrane lipids ALL INTERNALIZE BY ENDOCYTOSIS/PHAGOCYTOSIS
How are Lysosomal enzymes sorted when made?
Lysosomal enzymes are separated from other proteins in the TRANS-Golgi Network[TGN] by membrane-bound (mannose 6-phosphate receptors)–>then its collected in clathrin-coated vesicles
All Enzymes coming from the ER have _____-glycans BUT enzymes destined to be Lysosome Residents have a ________ sugar signal!
2)Are Lysosomes active when it receives this sugar signal in the ____?
ALL Enzymes coming from ER have N-linked glycans but…..
*Lysosomal Residents also have a
MANNOSE-6-PHOSPHATE sugar signal!
2)Lysosomes are NOT active when it receives its
[mannose-6-phosphate] signal in CIS-GOLGI, and only exist as pre-enzyme Zymogen.
»$Activation happens AFTER proteolytic cleavage in Lysosome
A: Describe mechanism for HOW the Lysosome Enzymes actually get their sugar signal in the cis-Golgi? [3]
B: Where do the enzymes that perform this “live”?
- Lysosome destined enzymes have special “signal PATCH” which binds to N-acetyl GlcNAC phosphotransferase enzyme—–>
- *transfers UDP-GlcNAC to the 6-OH of mannose———>
- **another enzyme then removes GlcNAC leaving JUST the mannose-6-phosphate on the lysosomal enzyme.
B: These enzymes that make this happen are cis-Golgi enzymes!
What is the function of endosomes when transporting enzymes from ____ to Lysosomes or _____?
in the TGN mannose-6-phosphate “marked” proteins are sorted for vesicular transport to endosomes—->which will then take it forward to Lysosomes or…
stay inside that endosome until it becomes a LATE ENDOSOME!
Transcytosis
Fairly common occurrence in which endocytosis occurs and take Cargo ACROSS a polarized cell, BYPASSING THE LYSOSOME to the other side, which would otherwise be impermeable!
[AKA INDIRECT sorting]
1) What would happen if N-acetyl glucosamine (GlcNAc) phosphotransferase is nonfunctional?? :-O [2]
2) How will this affect the cis-Golgi?
1)With no N-acetyl GlcNAC phosphotransferase the Lysosome signal PATCH will not be able to bind to start up process of getting its mannose-6-phosphate sugar signal for delivery to LYSOSOMES!
LYSOSOMAL enzymes stay in cis-Golgi INACTIVE and never make it to Lysosomes or LATE ENDOSOMES to do their work!
————————————————————————–
2)cis-Golgi will NOT be affected at this point since Lysosomal enzymes aren’t activated yet but eventually you’ll run out of active lysosomal enzymes
Explain the Proteolytic Processing of Lysosomal enzymes and secretory proteins
Lysosomal proteases acquire limited proteolytic activity within the low pH found in Lysosomes OR LATE ENDOSOMES–>activation of inactive lysosome Zymogens. Once activated, proteases are capable of processing even more inactive precursors!
Describe the 3 Main types of substrates for Lysosomal Degradation [What they are and How they get to Lysosome]
- BACTERIA=are phagocytosed and then tht phagosome fuses with lysosome to expose bact. to degradation
- EXTRACELLULAR SUBSTRATES= Receptor-Mediated endocytosis which bring molecules into endosomes
- ->eventually fuses w/lysosomes for degradation exposure - DYING OR DAMAGED ORGANELLES=
A: ER-derived membrane(originating from ER) thins out and then surrounds organelle->creates double membrane around organelle=AUToPHagy then…
B: AUToPHaGOSOME fuses w/lysosome which FIRST eats inner membrane and then eats Dying Organelle SECOND.
What are some physical “landmarks” of a Lysosome in the lab?
Lysosome have low pH, hydrolases and LAMPs
Polarized cells can sort Proteins from the ___ to the _______ or _____ domain of the plasma membrane.
*This is otherwise known as…..
Polarized cells sort Proteins from the trans-Golgi network to the basolateral or apical domain of the plasma membrane
*This is otherwise known as…DIRECT SORTING
1) What’s an effective way to bring in extracellular dead material for lysosome destruction?
2) What’s an example of this?
PHAGOCYTOSIS! At the completion of phagocytosis, the dead cell or organelle is surrounded by a SINGLE bilayer membrane so that it can fuse w/lysosome.
2) MACROPHAGES phagocytosizes RBC every second
How are lysosomal protein and enzymes given to pt who aren’t able to place a sugar signal on their own? [3]
synthetically tag synthetic lysosomal proteins/enzymes and inject them in pt to allow them to bind to pt mannose phosphate receptors
—->synthetic lysosome enzymes hops in clathrin coated vesicles which will fuse into Early Endosome–> will MATURE into a Lysosome
