Last Class:

1

• Last Class
• 1. transportation at the plasma membrane
• A. carrier protein, B. channel protein
• 2. intracellular compartments
• A. nucleus, B. Endoplasmic Reticulum

2

• Intracellular Vesicular Traffic

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The endocytic and biosynthetic-secretory pathways
4
Vesicular transport
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The intracellular compartments of the eucaryotic
cell in the biosynthetic-secretory and endocytic
pathways
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Utilization of different coats in vesicular
traffic
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Clathrin-coated pits and vesicles
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The structure of a clathrin coat
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The assembly and disassembly of a clathrin coat
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The role of dynamin in pinching off
clathrin-coated vesicles from the membrane
Shibire mutant in drosophila
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A current model of COPII-coated vesicle formation
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The postulated role of SNAREs in guiding
vesicular transport
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The structure of paired snare
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A model for how SNARE proteins may concentrate in
membrane fusion
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Dissociation of SNARE pairs by NSF after a
membrane fusion cycle is completed
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(No Transcript)
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A postulated role of Rab protein in facilitating
the docking of transport vesicles
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The entry of enveloped viruses into cells
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• Transport from the ER through the Golgi apparatus

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The recruitment of cargo molecules into ER
transport vesicles
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Retention of incompletely assembled antibody
molecules in the ER
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Vesicular tubular clusters
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A model for the retrieval of ER resident proteins
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The Golgi apparatus
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The functional compartmentalization of the Golgi
apparatus Notice of multiple steps involving
glycosylation
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Two possible models explaining the organization
of the Golgi apparatus and the transport of
proteins from one cisterna to the next
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• Transport from the trans Golgi nextwork to
  Lysosomes

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Lysosomes Low pH Full of Acid hydrolases
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The structure of mannose 6-phosphate on a
lysosome enzyme
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The transport of newly synthesized lysosomal
hydrolases to lysosomes
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• Transport into the cell from the plasma membrane
  endocytosis

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Phagocytosis by a macrophage Phagocytosis large
particle, gt250nm Pinocytosis fluid, liquid, 100
nm One macrophage and two red blood cells
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The formation of clathrin-coated vesicles from
the plasma membrane
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Caveolae in the plasma membrane of a fibroblast
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A low-density lipoprotein (LDL) particle
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Normal and mutant LDL receptor
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The receptor-mediated endocytosis of LDL
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Possible fates for transmembrane receptor
proteins that have been endocytosed
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Storage of plasma membrane proteins in recycling
endosomes
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Transcytosis
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Sorting of membrane proteins in the endocytic
pathway Green EGF-EGFR Red transferrin and its
receptor
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The sequestration of endocytosed proteins into
internal membranes of multivesicular bodies
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• Transport from the trans Golgi network to the
  cell exterior exocytosis

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The constitutive and regulated secretory pathways
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The three best-understood pathways of protein
sorting in the trans Golgi network
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Exocytosis of secretory vesicles
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Electron micrographs of exocytosis in rat mast
cells Release of histamine
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Exocytosis as a localized responses Beads
attachment localized the release
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Model of lipid rafts in the trans Golgi network
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The formation of synaptic vesicles
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Summary

• Intracellular vesicular traffic, SNARE, GAB,
  Clathrin, Dynamin, Adaptin
• ER-gtGolgi, COPII, COPI
• Golgi-gtlysosome, acid hydrolases, M6P
• endocytosis, phagocytosis, pinocytosis,
  clathrin-coated pit, caveolae,
• Exocytosis, constitutive and regulated mechanisms

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• Cell Signaling 1 General Concepts

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A simple intracellular signaling pathway
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Extracellular signaling molecules bind to
receptors
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Signals can be tranmitted either short or long
distances (I)
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Signals can be tranmitted either short or long
distances (II)
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For Long distance, two typical ways Endocrine
signaling Different cells need specific ligands
and receptors
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Synaptic signaling More efficient, same set of
ligands and receptors
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Signaling via GAP Junctions No ligand-receptor
system needed
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Combinatory effect of multiple inputs
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Different receptor type and intracellular
signaling molecules determine the ultimate
response
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Many signaling molecules have short lifetime
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NO (nitric oxide) induces the relaxation of
SMC The function of viagra is to inhibit cyclic
GMP phosphodiesterase, hence elongate the
lifetime of cyclic GMP and relaxation
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2 steps of responses may occur upon stimulation
Secon
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Cell Surface receptors belong to three classes
1. ion-channel-linked receptors, 2.
G-protein-linked receptors, 3. enzyme-linked
receptors
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Cell Surface receptors belong to three classes
1. ion-channel-linked receptors, 2.
G-protein-linked receptors, 3. enzyme-linked
receptors
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• Different Kinds of intracellular proteins serving
  as signaling molecules
• Relay proteins
• Messenger proteins
• Adaptor proteins
• Amplifier proteins
• Transducer proteins
• Bifurcation proteins
• Integrator proteins
• Latent gene regulatory proteins

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Two kinds of molecule switch events Phosphorylatio
n and GTP binding
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Signaling integration
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Intracellular signaling complexes enhance the
speed, efficiency, and specificity 2 types
Preassembled vs. Assembled after stimulation
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Intracellular signaling complexes enhance the
speed, efficiency, and specificity 2 types
Preassembled vs. Assembled after stimulation
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Binding domains for interactions between proteins
and complex assembly
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Cells can be sensitive to subtle difference in
environment 1. Multiple ligands are needed for
one signaling molecule
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Cells can be sensitive to subtle difference in
environment 2. Multiple ligated molecules are
needed to be assembled to be functional
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Cells can be sensitive to subtle difference in
environment 3. Positive feedback can enhance the
response drastically
76
Cells can adjust their sensitivity to stimuli by
desensitization process
77
Summary

• Typical signaling transduction pathway 1.
  ligand-receptor, 2. gap junctions
• Different inputs, receptors, intracellular
  signaling network determine the ultimate response
• The importance of lifetime of molecules
• Different steps of responses
• The types of receptors ion-channel-linked, G
  protein coupled, enzyme-linked receptors
• Intracellular signaling molecules, signaling
  switches, signaling integration, signaling
  complex assembly, protein-protein binding
  modulus, signaling amplification, signaling
  desensitization