Guillain-Barre syndrome (GBS) - PowerPoint PPT Presentation

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Guillain-Barre syndrome (GBS)

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1 ... active transport from cytosol to vesicles ... LDL: low density lipoprotein. Core ~1500 Cholesterol ester. Coat ~500 cholesterol ... – PowerPoint PPT presentation

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Title: Guillain-Barre syndrome (GBS)


1
GCCTCAATGGATCCACCACCCTTTTTGGGCAGCCTCAATGGATCCACCAC
CCTTTTTGGTGCAAGCCTCAATGGATCCACCACCCTTTTTGGTGCAAGCC
TCAATGGATCCACCACCCTTTTTGGTGCAAGCCTCAATGGATCCACCACC
CTTTTTGGTGCAAGCCTCAATGGATCCACCACCCTTTTTGGTGCAAGCCT
CAATGGATCCACCACCCTTTTTGGTGCAGCCTCAATGGATCCACCACCCT
TTTTGGGCAGCCTCAATGGATCCACCACCCTTTTTGGTGCAAGCCTCAAT
GGATCCACCACCCTTTTTGGTGCAAGCCTCAATGGATCCACCTCCACCAC
CCTTTTTGGTGCATGTGCCATGGC
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3
  • Gene expression
  • Transcription
  • Translation
  • Functional proteins post-translational
    modifications
  • Phosphorylation
  • Glycosylation
  • Sorting targeting to appropriate organelles
  • Modulation by extracellular signals
  • Covalent modification
  • Association with other molecules
  • Degradation

4
Sorting and Secretory pathways
  • diverged in trans-Golgi
  • Constitutive pathway
  • many soluble proteins
  • Regulated pathway
  • stored in secretory vesicles
  • active transport from cytosol to vesicles
  • complexed with macromolecules (e.g. proteglycans)

5
Regulated secretory pathway
  • In response to extracellular stimuli hormone,
    transmitters, digestive enzymes
  • stored in secretory vesicles
  • active transport from cytosol to vesicles
  • complexed with macromolecules (e.g. proteglycans)
    to reach high concentration

6
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Three pathways in Golgi
  • to lysosome
  • with mannose-6-phosphate, via late endosome to
    lysosome
  • to secretory pathways
  • Constitutive to apical or basolateral domain
  • Regulated

8
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9
Roadmap for traffic
  • Transport
  • Gated transport cytosol and nucleus via nuclear
    pore complexes
  • Membrane transport via membrane-bound
    translocators unfolded
  • Vesicle transport vesicles
  • Sorting signals

10
Membrane transport
  • Membrane-bound translocators
  • Unfolding of protein to be transported
  • Passing through a topologically distinct space
    cytosol to ER cytosol to mitochondria

11
Equivalent space for transport
  • Cycles of budding and fusion permits transport of
    molecules

12
Sorting signals
  • Signal sequences
  • 15-60 aa
  • Removed by signal peptidase when reaching the
    target
  • Signal patch
  • Usually non-continuous stretch of sequences
  • Exposed when appropriately folded

13
Sorting signals
14
Signal sequences
  • Function specify the direction for destination
  • for initial transfer to the ER with a signal
    sequence at N-terminus consisting of 5-10
    hydrophobic aa
  • Go forward Golgi most proteins
  • Return to ER (ER residents) with a specific
    sequence of 4 aa at C-terminus
  • Go to mitochondria positively charged amino
    acids alternate with hydrophobic ones
  • Go to peroxisome with a signal peptide of 3
    characteristic at C terminus

15
Signal sequences
16
Experiments to demonstrate zip code
  • Swap the signal sequence
  • e.g. adding the ER signal sequences to a
    cytosolic protein results in the retention of
    this protein in ER
  • Hyprophobicilty maybe a determing factor of
    signal sequences

17
Günter Blobel
18
Effect of misdirected protein
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20
Overview of protein sorting
21
Protein sorting
  • ER
  • ER-Golgi intermediate
  • Glogi network

22
Glycosylation in ER
23
Lysosomal protein phosphorylation of mannose
24
Sorting in Golgi
  • Export
  • Lysosome
  • Secretion
  • Constitute
  • Regulated
  • Retain in Golgi
  • transmembrane

25
Transport to plasma membrane
  • TGN
  • Apical domain
  • Basolateral domain

26
Endocytosis
  • Phagocytosis (cell eating)
  • Ingestion of large particles (e.g. bacteria)
  • In specialized cells
  • Pinocytosis (cell drinking)
  • Up-take of fluids or macromolecules in small
    vesicles
  • Receptor-mediated endocytosis
  • Common among eukaryotic cells

27
Phagocytosis
  • Pseudopodia
  • Phagosome
  • Phagolysosome

28
Receptor-mediated endocytosis
  • Clathrin-coated pits
  • Clathrin-coated vesicles
  • Example cholesterol, LDL, LDL receptor

29
LDL low density lipoprotein
  • Core
  • 1500 Cholesterol ester
  • Coat
  • 500 cholesterol
  • 800 phospholipid
  • 1 Apoprotein B100

30
LDL receptor
  • MS Brown, JL Goldstein
  • Familial hypercholesterolemia
  • LDL-binding domain
  • Internalization signal

31
LDL receptor
  • Internalization signal Tyr

32
Clathrin-coated pits
33
Lysosomal proteins in clathrin-coated pits
34
Sorting in early endosome
  • Acidic ph by H pump for dissociation of proteins

35
Recycling of synaptic vesicles
36
Protein sorting by transcytosis
  • Membrane protein in apical domain
  • Secretory proteins from bloodstream

37
Lysosomal system
  • For membrane-bound proteins and proteins taken by
    endocytosis
  • Multiple acid proteases (cathepsins) and other
    hydrolases
  • Studied with weak bases to inhibit lysosomal
    acidification or lysosomal inhibitors (E64)
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