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pH is one of the mechanismsfor protecting contents in the cytosol
Vacuolar H+ ATPase:
LysosomesEndosomesSelected compartments ofGolgi ApparatusTransport vesiclesSecreted vesicles
All major classes of macromolecules are degradedin lysosomes
Lysosomal glycoproteinsare unusually highly glycosylated
40 hydrolytic enzymes
Lysosomes are highly heterogeneousShape and size
But all have acid hydrolases
The “stomach” of a cell
Stained for acid phosphatase:Phosphatase substrate
Huge vacuoles of plant cells
Related to lysosomes
Storage organelle
Degradative compartments
Turgor pressure
Homeostatic device
RubberOpiumGarlicProteinsPigmentsNoxious molecules
The transport of newly synthesized lysosomal hydrolases to lysosomes
M6P receptor
pH6.5-6.7pH6.0
Recycling of M6P
Lysosomal storage diseases
Some lysosomes may undergo exocytosis
A signal patch in the hydrolase polypeptide chain provides the cue for M6P addition
Defects in the GlcNac phosphotransferase cause alysosomal storage disease in humans, inclusion-cellDisease (I-cell disease)
N-acetylglucosamine
Phagocytosis by a macrophate Phagocytosis by a neutrophil
Pinocytosis: cell drinking; Phagocytosis: cell eating
pseudopods
A low-density lipoprotein(LDL) particle
Receptor-mediated Endocytosis
Example: cholesterol uptake
Atherosclerotic plaques;When uptake is blocked
Atherosclerosis
3,000 Kd1500 cholesterolMolecules800 phospholipid500 unesterified cholesterol
500 Kd
Cholesterol estersAre hydrolyzed to Free choleterol in lysosomes
Normal and mutant LDL receptor
Coronary artery disease
Common endocytic signal: YXXbinding to adaptin)But LDL receptor:Asn-Pro-Val-Tyr
Possible fates for transmembrane receptor proteins
Different Rabsassociate withearly and lateendosomes
Recycling:LDL receptor
Sorting of transferrin (red)and opioid receptors (green)in the recycling endosomes
Transferrin receptor recycles withits ligand
DifferentRabs
Opioid receptors and EGF receptorsAre not recycled but degraded inLysosomes along with ligand: receptorDown-regulations
Some early endosomes Migrate slowly along MTToward the cell interiorAnd pinch off Vesicles to form MVBs
MVBs may fuse with a lateendosomal compartment orthey fuse with each otherto become late endosome
Receptors and their ligandsare fully accessible to digestive enzymes in MVBs
Ubiquitin tagging facilitatethe uptake of receptors into endocytic vesicles andand sorting into theinternal membrane vesiclesof MVBs
Transcytosis: transferring macromolecules across ephithelial cell sheets
Remember transcelluartransport of glucose?
Early endosome torecycling endosome
Receptors havesorting signals
A newborn rat obtains antibodies from its mother’s milk
Secretory proteins formselective aggregates
Secretory proteins becomehighly concentrated:aggregation and membraneretrieval
Proteins are often proteolytically processed during the formation of secretory vesicles
Size of the final products
Activity
In different cells
A prohormone
Regulated exocytosis can be a localized response of the plamsa membrane and its underlying cytoplasm
Mast cellsecreting histamineall over thecell surface whenon a solution ofsoluble stimulant
Localized exocytosis whenstimulant is presented from asolid bead
Two types of polarized cells
Polarized cells direct proteinsfrom the trans Golginetwork to the appropriatedomain of the plasma membrane
Lipid rafts in the trans Golgi networkGlycosphingolipids and cholesterol form rafts in the lipid bilayer
May mediate sorting of glycosphingolipids and GPI-anchored proteinsTo the apical plasma membrane
Summary
1. Lysosomes are where most of the intracellular degradationoccurs. Formation of lysosomes, sorting into lysosomes;
2. Phagocytosis, pinocytosis, receptor-mediated endocytosis,early endosomes, late endosomes, recycling endosomes;
3. Two types of exocytosis, sorting during exocytosis, synapticvesicles.
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