medcelična signalizacijabio.ijs.si/~krizaj/group/predavanja 2010/medcelicna signalizacija... ·...
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Medcelična signalizacija -
- prenos živčnega signala
Lodish, H. et al.: Nerve cells. In: Molecular cell biology, W.H. Freeman & Co., New York.
Alberts, B. et al.: Membrane transport of small molecules and the electrical properties of membranes. In: Molecular Biology of the Cell, Garland Science, New York.
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Structure of typical mammalian neurons
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Hippocampalinterneurons
green - MAP2
red - synaptotagmin
Neurons communicate with many other cells
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A synapse
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Reception, conduction and transmissionof electric signals
Ion channels in neuronal plasma membrane:
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Origin of the resting PM potentialin a typical vertebrate neuron
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Electric potential across the cell PM
Nernst equation:
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Effect of changes in ion permeabilityon PM potential
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Passive spread of a depolarization of a neuronal PMwith only resting K+ ion channels
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Voltage-gated ion channels generate action potentials(cycles of membrane depolarization,
hyperpolarization, and return to the resting potential)
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Ion permeabilities during an action potential
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Structure and function of the voltage-gated Na+ channel
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Unidirectional conductionof an action potential
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Myelination of axons
50-100 membrane layers
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Formation and structure of a myelin sheath
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Myelination increases thevelocity of signal conductionfrom ~1 m/s to 10-100 m/s.
12 µm myelinated vertebrate axon600 µm unmyelinated squid axon
12 m/s
Radical reduction of neuronal volume
Evolution of vertebrate brain
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Signal transmission at a chemical synapse(frog neuro-muscular junction)
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A chemical synapse - schematically
~20 nm
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Neurotransmitters
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Synaptic vesicle cycle
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Excitatory and inhibitory responses in postsynaptic cells
Frog skeletal muscle- nicotinic AChR(ligand-gated ion channel)
Frog heart muscle- muscarinic AChR(G protein-coupled R)
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Activation of ligand-gated ion channels at a NM junction
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Nicotinic ACh receptor
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Fast synapses
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Muscarinic ACh receptor (M2)in the heart muscle PM
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Slow synapses
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An electric synapse - schematically
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Ukrivljanje membran
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McMahon & Gallop (2005) Nature 438, 590-596.
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Mechanisms of membrane deformation
McMahon & Gallop (2005) Nature 438, 590-596.
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Phospholipids have different shapes andlipid shape affects membrane curvature
Inverted-cone Cone
Sprong et al. (2001) Nat. Rev. Molec. Cell. Biol. 2, 504-513.
PSMS
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Lipid shapingPalmitoyl CoA
CtBP/BARS
Scales & Scheller (1999) Nature 401, 123-124.
- Enzymes that change lipid headgroup size- Flippases
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Mechanisms of membrane deformation
McMahon & Gallop (2005) Nature 438, 590-596.
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Amphipatic helix and membrane curvature
McMahon & Gallop (2005) Nature 438, 590-596.
BAR domains
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Role of LPAAT-mediated conversion of LPA to PAin one of the steps of synaptic vesicle formation (fission)
Schmidt et al. (1999) Nature 401, 133-141.
LPAAT
LPAAT
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Recommended reading:Chen, Y.A. and Scheller, R.H. (2001): SNARE-mediated membrane fusion.
Nat. Rev. Mol. Cell Biol. 2, 98-106 Gallop, J.L. et al. (2005): Endophilin and CtBP/BARS are not acyl transferases in endocytosis
or Golgi fission. Nature 438, 675-678. Huttner, W.B. and Zimmerberg, J. (2001): Implications of lipid microdomains for
membrane curvature, budding and fission. Curr. Opin. Cell Biol. 13, 478-484Huttner, W.B. and Schmidt, A.A. (2002): Membrane curvature: a case of endofeelin`…
Trends Cell Biol. 12, 155-158Ikonen, E. (2001): Roles of lipid rafts in membrane transport. Curr. Opin.
Cell Biol. 13, 470-477McMahon, H.T. and Gallop, J.L. (2005): Membrane curvature and mechanisms of dynamic
cell membrane remodelling. Nature 438, 590-596Peters, C. et al. (2001): Trans-complex formation by proteolipid channels in the terminal
phase of membrane fusion. Nature 409, 581-588Ringstad, N. et al (1999): Endophilin/SH3p4 is required for the transition from early to
late stages in clathrin-mediated synaptic vesicle endocytosis. Neuron, 24, 143-154Scales, S.J. and Scheller, R.H. (1999): Lipid membranes shape up.
Nature 401 ,123-124Schmidt, A. et al. (1999): Endophilin I mediates synaptic vesicle formation by transfer of
arachidonate to lysophosphatidic acid. Nature 401, 133-141Weigert, R. et al. (1999): CtBP/BARS induces fission of Golgi membranes by acylating
lysophosphatidic acid. Nature 402, 429-433