Lecture 14 Vesicular Transport II Flashcards
what are the membrane compartments of lysosome filled with
hydrolytic enzymes
what is the function of lysosomes
intracellular digestion of macromolecules
what type of enzymes are found in lysosomes
proteases nucleases gylcosidases lipases phospholipase phosphates sullfatases
what do lysosomes require for optimal activation
acidic environment
proteolytic cleavage
vacuolar ATPase
pumps H+ into lysosomes to maintain acidic pH and drive transport of small metabolites
what does the Trans-Golgi network deliver to lysosomes
membrane proteins and hydrolyses
steps in co-translation transport of membrane proteins and hyrolases to lysosome in TGN
into rough Er
then transported via Golgi comes to TGN
TGN buds off Golgi to form
endosomes
these develop into lysosomes
what do lysosomal hydrolyses have that attach them in the CGN
sorting signal
sorting signal of lysosomal hydrolyses
Mannose 6 Phosphate
what do M6P receptors in TGN recognize
sorting signal sugar, M6P
after hydrolyses bind to TGN…
they are packaged into clathrin coated vesicles that bud off and delivered to endosomes then lysosomes
steps of lysosomal protein sorting
transport of newly synthesized lysosomal hydrolases to lysosomes
- on cis-Golgi mannose binds to hydrolase from ER and phosphate is added – becomes M6P
- M6P signal is uncovered as it moves thru Golgi
- M6P binds to M6P receptor, gets clathrin coated and buds off
- Transport to endosome, fusion with endosome
- hydrolyses dissociate from M6P receptors (due to low pH)
- Empty transports are recycled back to the TGN
- in endosomes, phosphate is removed and hydrolyses are kept in the endosome
what is the enzyme responsible for recognizing the lysosomal hydrolase?
GlCNAc phosphotransferase
how does the lysosome recognize the hydrolase
signal patch binds to the phsphotransferase
binding site of phosphotransferase binds
high mannose N-linked oligosaccharides
UDP-GLCNAc
steps in lysosomal recognition
- binding of signal path to recognition site of phosphotransferase
- transfer of GlcNAc-P to mannose at catalytic site
- release
- remold of GLcNAc
lysosomal storage disease
caused by genetic defects in lysosomal hydrolyses
results in accumulation of undigested material in lysosome
Inclusion Cell disease
Hurlers Disease
Missing GlcNAc phosphtransferase