The origin of the nervous system_A molecular perspective

The origin of the nervous system_A molecular perspective -...

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The Origin of the Nervous System: a molecular perspective. Where do the genes for ion channels and receptors come from? Did they exist before there was a nervous system? How was the node of Ranvier formed? The role in genome duplication (ploidy) in shaping the vertebrate genome.
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N C + S 1 S 2 S 3 S 4 S 6 S 5 + N C + S 1 S 2 S 3 S 4 S 6 S 5 + N C + S 1 S 2 S 3 S 4 S 6 S 5 + N C + S 1 S 2 S 3 S 4 S 6 S 5 + N C + S 1 S 2 S 3 S 4 S 6 S 5 + N C + S 1 S 2 S 3 S 4 S 6 S 5 + M 2 1 N C N C + S 1 S 2 S 3 S 4 S 6 S 5 + N C + S 1 S 2 S 3 S 4 S 6 S 5 + + H 3 N + S 1 S 2 S 3 S 4 S 6 S 5 + + S 1 S 2 S 3 S 4 S 6 S 5 + + S 1 S 2 S 3 S 4 S 6 S 5 + CO 2 - + S 1 S 2 S 3 S 4 S 6 S 5 + O u ts ide Ins ide M 2 M 1 N C + H 3 N CO 2 - Kir1  Kir2  Kir3  Kir4  Kir5  Kir6  Kir7  nIRK Kir3.1    Kir  3.2    Kir  3.3    Kir  3.4 Kv1  Kv2  Kv3  Kv4 Kv1.1, Kv1.2, Kv1.3, Kv1.4, Kv1.5, Kv1.6, Kv1.7, Kv1.8 Sodium & Calcium voltage-gated KQT eag slo CNG Novel > 23 genes K+ channels K+ channels KVLQT KVLQT2 eag erg elk slo slo2/slack Superfamily Inward rectifier K + channels Voltage-dependent K + channels K+ Leak channels
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Evolution of ion channels M 2 M 1 N C N C + S 1 S 2 S 3 S 4 S 6 S 5 + Leak K + channel: single pore (S5-P loop-S6) Voltage-dependent K + channel: S1-S4 (S4 = voltage sensor) K + channels evolved in bacteria: found in all organisms Form a tetramer: it takes 4 of them to make a complete channel.
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Evolution of ion channels Ca 2+ channels: two rounds of gene duplication led to single channel with 4 repeating domains. First appeared in single celled eukaryotes + H 3 N + S 1 S 2 S 3 S 4 S 6 S 5 + + S 1 S 2 S 3 S 4 S 6 S 5 + + S 1 S 2 S 3 S 4 S 6 S 5 + CO 2 - + S 1 S 2 S 3 S 4 S 6 S 5 + O u ts ide Ins ide One molecule makes a single channel
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Ion Channel Structure 4 subunits form tetramer Single protein forms channel
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?
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Structure of a Na + channel
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Reconstructing the metazoan “channelome” How did the ion channel types of single celled eukaryotes diversify into the types observed in bilateria? When did Na + channels arise? When did Ca 2+ channels diversify? L type--muscle T type--heart N/P/Q type--synaptic transmission
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Monosiga Trichoplax Nematostella Bilateria Note: organisms not drawn to scale.
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Liebeskind et al. 2011
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The four domains of the Na + channel cluster to form an ion-permeant pore. D E K A
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The pore is intermediate between a Ca 2+ channel and a Na + channel
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The pore is intermediate between a Ca 2+ channel and a Na + channel
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What is the origin of some neurotransmitter receptors? Glutamate receptors: ionotropic, metabotropic.
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