Membrane Traffic 1 and 2

Membrane Traffic 1 and 2

Membrane Traffic 1 and 2

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Proteins

  • Proteins on the membrane - not just plasma membrane
  • A lot of receptors/channels are drug targets

Plasma Membrane

Lipids in Cellular Membranes

Lipid Rafts

Lipids are Asymmetrically Organised

Endocytosis

  • Internalisation of very important molecules
  • Cell uptake of extracellular nutrients 
  • Iron - transferrin - transferrin receptor
  • Fats - LDL via LDL receptor
  • Proteins - for degredation, downregulation of oncogenic signals - cancer
  • Cell recovery through endocytic recycling - protens and lipids
  • Cholesterol homeostasis
    • LDL receptor
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Endocytosis

  • 1 - macropinocytosis
  • 2 - clathrin coated vesicles
  • 3 - clathrin independent endocytosis
  • 4 - clavaeolae - platform is lipid raft
  • 5 - phagocytosis

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Material is taken into cells in clathrin coated ve

Endocytosis and pH

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Lysosome - The Acidic Cell Stomach

Receptor Mediated Endocytosis

  • Transferrin binding to transferrin receptor
  • Epidermal growth factor (EGF) binding to EGF receptor
  • LDL binding to LDL receptor
    • benefits to the cell
    • endocytic pathway transversed by receptor and ligand
  • All these rely on clathrin mediated endocytosis
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Iron

  • Anaemia - too low
  • Haemochromatosis - too high

Receptor Mediated Endocytosis of Epidermal Growth

Lipid Transportation in Cells - Hyperlipidaemias

  • Fats being hydrophobic need specialised transport
    • Lipoprotein complexeds (endogenous fats)
  • Products of digestion carried by proteins
    • Triglycerides --> beta-globulins
    • Cholesterol --> beta-globulins and synthesised in the body
    • Phospholipids --> alpha-globulins
    • Free fatty acids --> albumins
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Plasma Lipids and Lipid Transport

  • Insoluble - need to be transported
    • for solubility
    • for recognition
  • Free fatty acids bound to the plasma protein albumin
  • Cholesterol, triglycerides and phospholipids are transported as lipoprotein complexes
    • Proteins associated with them are called apoproteins
      • Major apoproteins - APO E, APO C, APO B
  • LDL - very important lipoprotein complex
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Receptor Mediated Endocytosis of LDL Receptor

Phagocytosis and Autophagy

  • Phagocytosis - cell eating from the outside
    • Immune cells - macrophages, neutrophils, dendritic cells
  • Autophagy - eating from the inside
    • Old and damaged organelles are wrapped in membrane and derived to lysosomes for degradation
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The Secretory Pathway

  • Delivery of membrane proteins
    • Transferrin receptor
    • CFTR
    • LDL receptor
  • Soluble proteins via exocytosis
    • Insulin (hormone), pepsin
    • Small molecules via exocytosis
    • Neurotransmitters - acetylcholine and noradrenaline 
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Proteins travel from endoplasmic reticulum in vesi

Insulin

The first:

  • hormone isolated from animal source in a form that could be administered therapeutically to humans
  • hormone to have its mechanism of action elucidated
  • hormone to have its primary and secondary structure determined
  • hormone to be measured using radioimmunoassay
  • hormone discovered to be processed as a larger immature form
  • hormone to be synthesised using recombinant DNA technology - bacteria E.coli
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Insulin

Membrane Traffic and Disease

  • There are many hundreds of diseases associated with membrane traffic
  • Examples:
    • Cystic fibrosis - indirect
      • Traffic of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)
    • Niemann Pick Type (NP-C) - direct
      • Defects in transport of lipids to lysosomes
      • A lysosomal storage disease
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CFTR transport blocked in endoplasmic reticulum

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