Bio 103 Lecture

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Bio 103 Lecture 9READINGSIntro to
lysosomes 5165-168Receptor-mediated
endocytosis 17 727-735

• Protein Sorting III
• Endocytosis (Lysosomes)

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Protein Sorting III Endocytosis (Lysosomes)

• I. All eukaryotic cells undergo endocytosis
• II. Endocytic pathway for LDL

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Protein Sorting III Endocytosis (Lysosomes)

• I. All eukaryotic cells undergo endocytosis
• -internalizing material from surroundings
• -types endocytosis
• phagocytosis (pinocytosis)
• autophagy
• receptor-mediated endocytosis
• EXAMPLE Low Density Lipoprotein (LDL)

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13-35 (Alberts) Three pathways to degradation in
lysosomes

• Mutilple pathways deliver materials (derived from
  different sources) to lysosomes
• Endocytosed vesicles mature from vesicles to
  early endosomes to late endosomes to lysosomes

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17-1 Overview of the secretory and endocytic
pathways of protein sorting

• Lysosomal function requires
• hydrolytic enzymes (delivered from TGN)
• Materials to be digested (derived from
  endocytosis)
• NOTE secretory and endocytic pathways converge
  in lysosome!

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Protein Sorting III Endocytosis (Lysosomes)

• I. All eukaryotic cells undergo endocytosis
• II. Receptor mediated endocytic pathway for LDL
• -cell-surface LDL-receptors bind LDL particle
• -clathrin coated pits containing receptor-LDL
  pinch off
• -coat is shed
• -uncoated vesicle fuses with late endosome (low
  pH causes disassociation of LDL and receptor)
• -late endosome fuses with lysosome, LDL proteins
  and lipids broken down
• -LDL receptor recycles to cell surface

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What is LDL?

• Cells acquire cholesterol from the diet
• Cholesterol is carried in the bloodstream in
  particles called low-density lipoprotein (LDL)
  particles
• A LDL particle consists of
• outer phospholipid shell with a single surface
  protein (apoB-100)
• core of cholesterol molecules
• Mammalian cells produce cell-surface receptors to
• apoB-100 and internalize the LDL particle by
• receptor-mediated endocytosis
• LDL particles are broken down in the lysosome,
  the cholesterol molecules are then available to
  be used by the cell

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17-27 Initial stages of receptor-mediated
endocytosis of LDL particles
A. Coated pit, B. pinching off of coated vesicle,
C. coated vesicle diffusing towards target, D.
LDL arrives in early endosome (6 minutes after
internalization began)
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17-28 Endocytic pathway for internalizing LDL

• LDL receptors bind aboB protein embedded in
  phospholipid outer layer of LDL particle
• Clathrin-coated pits pinch off
• Uncoated vesicle (now called early endosome)
  fuses with late endosome. Acidic pH causes
  receptor to release LDL particle
• Late endosome fuses with lysosome, LDL particle
  hydrolyzed into constituent parts
• LDL receptor recycles to cell surface

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17-29 EM demonstrates that endocytosed
receptor-ligand complexes disassociate in the
late endosome
NOTE ligand is located in vesicle lumen,
receptor is localized to tubular extensions
budding off vesicle
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17-30 Model for pH dependent binding of LDL
particles by the LDL receptor (cell surface)
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17-31Q How do endosomes / lysosomes hydrolyze
membrane-bound proteins?

• A Endosomes bud inward, creating a
  multi-vesicular endosome with internal vesicles
• Inward vesicularization utilizes endosomal
  sorting complex (ESCRT) proteins
• HIV redirects/hijacks ESCRT proteins to cell
  surface to facilitate viral budding