93' StructureFunction of the Organelles Synthesis

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9-3. Structure/Function of the Organelles
Synthesis
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Types of Vesicle Transport

• COPII-coated vesicles
• Select and concentrate transport components
• Integral membrane proteins of the ER
• Enzymes acting at a later stage
• Membrane proteins docking and fusion
• Membrane proteins binding soluble cargo
  secretory proteins

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Types of Vesicle Transport

• COPI-coated vesicles
• Proteins of ER have C-terminal retrieval sequence
• Specific receptors
• Soluble ER proteins typically have - KDEL
• KDEL receptor cytosolic domain binds to the
  COPI coat

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Types of Vesicle Transport

• COPI-coated vesicles
• Integral membrane proteins of ER
• SRP receptor
• KKXX

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Targeting Vesicles

• Movement of the vesicle target
• Microtubules railroad tracks to a specific
  target

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Targeting Vesicles

• Tethering of the vesicle
• Specific binding via Rabs
• Docking
• Proteins called SNAREs
• Integral membrane proteins
• Localized to specific sub-cellular compartments
• Two categories

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Targeting Vesicles

• SNAREs
• Two categories
• v-SNAREs transport vesicle membrane
• t-SNAREs target compartment membrane

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Targeting Vesicles

• SNAREs
• (1)

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Targeting Vesicles

• SNAREs
• (2)

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Lysosomes

• Digestive organelles
• 50 hydrolytic enzymes
• Every macromolecule class
• Low molecular wt. products to cytosol
• All with optimum pH acidic 4.6
• Acid hydrolases
• H concentration proton pump
• Membranes contain specialized proteins
• Highly acidic
• Highly glycosylated

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Lysosomes

• Functions
• Mammals
• Macrophages / neutrophils

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Lysosomes

• Functions
• Organelle turnover
• Autophagy
• Residual bodies
• Lipofuscin granules

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Endocytosis

• Two categories
• Bulk-phase endocytosis
• Non-specific uptake
• Receptor-mediated uptake
• Specific molecules (ligands)
• Dynamic and rapid process

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Endocytic Pathway

• Well defined network of endosomes
• Highly acidic proton pump
• Two classes
• Early endosomes
• Late endosomes

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Endocytic Pathway

• Early endosomes
• Sorting function
• Integral membrane proteins
• Dissociate from ligands
• Recycled back to plasma membrane

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Endocytic Pathway

• Late endosomes
• Materials directed to a lysosome

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Endocytic Pathway

• Receptor-mediated endocytosis
• Means for uptake of macromolecules present in low
  concentrations
• Receptors collect in the plasma membrane
• Specialized areas coated pits

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Endocytic Pathway

• Receptor-mediated endocytosis
• Coated pits
• Clathrin molecule
• Three heavy chains
• Three light chains
• Triskelion
• Contain adaptor complexes
• Engage cytoplasmic domains of membrane receptors

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Endocytic Pathway

• Receptor-mediated endocytosis

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Endocytic Pathway

• A special example LDLs and cholesterol
  metabolism
• Cholesterol is hydrophobic
• Transported in blood as huge lipoprotein
  complexes
• Eg low-density lipoprotein (LDL)

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Endocytic Pathway

• LDL
• Core 1500 cholesterol molecules
• Esterified to long-chain fatty acids
• Core is surrounded
• Single layer phospholipids / free cholesterol /
  alipoprotein B-100

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Endocytic Pathway

• Alipoprotein B-100
• Binds LDL receptors on cell membranes
• LDL bound to coated pit
• Invaginates coated vesicle
• Receptors recycled to membrane
• LDL - lysosomes

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Endocytic Pathway

• LDL in blood
• Highly correlated with artherosclerosis
• LDL-containing plaques in vessel walls
• Initiated by injury to vascular endothelial cells
• MØ infiltrate
• Endocytose LDL
• Foam cells
• MØ induce smooth muscle to produce connective
  tissue
• Bulges into the lumen

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Endocytic Pathway

• HDL
• Carry cholesterol back to the liver
• Associated with decreased risk of artherosclerosis