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. 1
Structure of typical mammalian neurons 2
Neurons communicate with many other cells green -MAP2 Hippocampal interneurons red - synaptotagmin 3
A synapse 4
Reception, conduction and transmission of electric signals Ion channels in neuronal plasma membrane: 5
Origin of the resting PM potential in a typical vertebrate neuron 6
Electric potential across the cell PM Nernst equation: 7
Effect of changes in ion permeability on PM potential 8
Passive spread of a depolarization of a neuronal PM with only resting K + ion channels 9
Voltage-gated ion channels generate action potentials (cycles of membrane depolarization, hyperpolarization, and return to the resting potential) 10
Ion permeabilities during an action potential 11
Structure and function of the voltage-gated Na + channel 12
Unidirectional conduction of an action potential 13
Myelination of axons 50-100 membrane layers 14
Formation and structure of a myelin sheath 15
Myelination increases the velocity of signal conduction from ~1 m/s to 10-100 m/s. 12 µm myelinated vertebrate axon 600 µm unmyelinated squid axon 12 m/s Radical reduction of neuronal volume Evolution of vertebrate brain 16
Signal transmission at a chemical synapse (frog neuro-muscular junction) 17
A chemical synapse - schematically ~20 nm 18
Neurotransmitters 19
Synaptic vesicle cycle 20
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) 21
Activation of ligand-gated ion channels at a NM junction 22
Nicotinic ACh receptor 23
Fast synapses 24
Muscarinic ACh receptor (M2) in the heart muscle PM 25
Slow synapses 26
An electric synapse - schematically 27
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Ukrivljanje membran 29
McMahon & Gallop (2005) Nature 438, 590-596. 30
Mechanisms of membrane deformation McMahon & Gallop (2005) Nature 438, 590-596. 31
Phospholipids have different shapes and lipid shape affects membrane curvature Inverted-cone MS PS Cone Sprong et al. (2001) Nat. Rev. Molec. Cell. Biol. 2, 504-513. 32
Lipid shaping Palmitoyl CoA CtBP/BARS Scales & Scheller (1999) Nature 401, 123-124. - Enzymes that change lipid headgroup size -Flippases 33
Mechanisms of membrane deformation McMahon & Gallop (2005) Nature 438, 590-596. 34
Amphipatic helix and membrane curvature BAR domains McMahon & Gallop (2005) Nature 438, 590-596. 35
Role of LPAAT-mediated conversion of LPA to PA in one of the steps of synaptic vesicle formation (fission) LPAAT LPAAT Schmidt et al. (1999) Nature 401, 133-141. 36
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, 478-484 Huttner, W.B. and Schmidt, A.A. (2002): Membrane curvature: a case of endofeelin` Trends Cell Biol. 12, 155-158 Ikonen, E. (2001): Roles of lipid rafts in membrane transport. Curr. Opin. Cell Biol. 13, 470-477 McMahon, H.T. and Gallop, J.L. (2005): Membrane curvature and mechanisms of dynamic cell membrane remodelling. Nature 438, 590-596 Peters, C. et al. (2001): Trans-complex formation by proteolipid channels in the terminal phase of membrane fusion. Nature 409, 581-588 Ringstad, N. et al (1999): Endophilin/SH3p4 is required for the transition from early to late stages in clathrin-mediated synaptic vesicle endocytosis. Neuron, 24, 143-154 Scales, S.J. and Scheller, R.H. (1999): Lipid membranes shape up. Nature 401,123-124 Schmidt, A. et al. (1999): Endophilin I mediates synaptic vesicle formation by transfer of arachidonate to lysophosphatidic acid. Nature 401, 133-141 Weigert, R. et al. (1999): CtBP/BARS induces fission of Golgi membranes by acylating lysophosphatidic acid. Nature 402, 429-433 37