matching proteins and receptors

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How would you ensure that a particular
protein would get put into a particular vesicle?

• matching proteins and receptors

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SNARE Proteins Involved in Vesicle Fusion

• SNAREs are integral proteins with cytoplasmic
  helical domains
• many different SNAREs (membrane/organelle
  specific)
• upon contact, helical domains intertwine forming
  trans-SNARE complex and resulting stable locking
  of vesicle and target membranes

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SNARE Proteins Involved in Vesicle Fusion
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Rabs Make Vesicle-Target Docking Specific
1. Rabs are GTPases (GTP-binding proteins) 2.
membrane/organelle specific 3. recruit specific
proteins in cytosol that tether vesicle Rab to
membrane Rab (at least 60 distinct Rabs in humans)
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Three Coat Proteins of Vesicular Traffic

• COPII coats vesicles that transport proteins
  from rough ER to cis-Golgi
• COPI coats vesicles that transport proteins in
  retrograde direction between Golgi cisternae and
  from cis-Golgi to rough ER
• clathrin coats vesicles that transport proteins
  from plasma membrane and trans-Golgi to late
  endosomes

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Three Coat Proteins of Vesicular Traffic
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Clathrin-Coated Vesicle Formation
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A Closer Look At Clathrin-Coated Vesicles
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Clathrin-Coated Vesicle
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Clathrin-Coated Vesicles
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Dynamin Pinches off Clathrin-Coated Vesicles
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Dynamin Pinches off Clathrin-Coated Vesicles
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Lysosomal Enzymes Transported to Lysosomes

• mannose residues phosphorylated
• incorporated into clathrin-coated vesicle
• mannose 6-phosphate receptors interact with
  lysosomal enzymes inside and adaptors outside
  vesicle
• MPR returned to Golgi
• MPR in plasma membrane capture secreted lysosomal
  enzymes

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Pathways to Lysosomes
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Endocytic Pathway
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Receptor-Mediated Endocytosis
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Phagocytic Pathway
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Phagocytosis
20
How do you think a phagocyte distinguishes between
foreign cells and the bodys own cells?

• antigens on foreign cells, our bodies make
  antibodies, antibodies cover foreign cells,
  antibodies are tag that phagocytes recognize as
  tag for destruction

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Autophagic Pathway
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Autophagy
23
Why would a cell want to destroy its own
organelles?

• old or dysfunctional organelles need to be
  destroyed so cell is working efficiently and
  properly

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Lysosomes Sites of Intracellular Digestion
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Lysosomes Sites of Intracellular Digestion

• membrane-enclosed compartments filled with
  hydrolytic enzymes (40 acid hydrolases)
• intracellular digestion of almost every type of
  biological macromolecule
• require interior pH of 5.0 for proper function
• H-ATPase pumps H into lysosome
• membrane proteins transport digestion to cytosol,
  these proteins are highly glycosylated to protect
  them from degradation
• very heterogeneous

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Lysosomal Proton Pump
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Lysosomal Storage Disorders
Deficiency of a single lysosomal enzyme results
in the accumulation of an undegraded substrate.
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Tay-Sachs Disease

• genetic disease found in French Canadians of
  Southeastern Quebec, Cajuns of Southwest
  Louisiana, and Ashkenazi Jews
• affected individuals have absent or reduced
  amounts of hexosaminidase A
• results in excessive accumulation of GM2
  ganglioside in neurons
• infantile and juvenile forms cause blindness,
  paralysis, dementia, and early death
• chronic adult form exhibits neuron dysfunction
  and psychosis