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184 117 P Thiel 1 1 2 2 2 3 2 1 1 2 2 3 Thiel Graz Dr. Thiel Thiel 16 8 Thiel 4 Thiel Thiel P 1 1 2 2 1 1 1 1 1 1 2 2008 FA 0.1 ppm FA FA 20 FA FA FA B 0.1 ppm B FA FA 0.1 ppm FA 0.1 ppm FA P 1 2,3 2,3,4 1 4 2 3 4 6 Hedgehog Hedgehog SmoothenedSmo Smo 9 cKO SmocKO SmocKO P 1 1 2 2 2 3 3 3 3 1 4 2 3 3 PF PF Cholera toxin b subunitCTb CTb cFos mapping CTb CA1 C1 CTb cFos P Tubulin polyglutamylation regulates cytoskeletal distribution in brain Kenji Ohata 1 , Yoshiyuki Konishi 2 , Reiko Tsuchiya 3 , Koji Ikegami 1 , Mitsutoshi Setou 1 1 Dept. of Cell Biology and Anatomy, Hamamatsu Univ. Sch. of Med., 2 Dept. of Human and artificial intelligent Systems, Univ. of Fukui, 3 MitsubishiKagaku Institute of Life Sciences Microtubules form the structural basis of neuronal morphology and partake in directing intracellular transport. Tubulins, components of microtubules, are known to be highly polyglutamylated in neurons, and we, along with another group, have recently shown that a part of tubulin tyrosine ligaselike Ttll proteins catalyzes polyglutamylation of tubulins though the subsequent function of this polyglutamylation remains unclear. Present study demonstrates that Ttll1 and Ttll7 play major roles in adding glutamate chain to alpha and beta tubulin respectively in the brain. Ttll1 or Ttll7 singleknockout mice exhibited only a slight decrease in total polyglutamylation. To reveal the neuronal polyglutamylation function, we generated Ttll1Ttll7 doubleknockout mice which showed significant decrease in neuronal polyglutamylation. Immunohistochemical and electron microscopic analyses showed fewer neurofilaments in dendrites of cortical neurons in the doubleknockout mice compared to the wild type, while the neurofilament distribution in Ttll1 or Ttll7 singleknockout mice was similar to that of the wild type. These results suggest that polyglutamilation regulates neurofilament arrangement. P KCC 1 2 1 2 3 KCC2 Cl – GABA KCC2 in situ hybridization in situ hybridization KCC2 mRNA 5 P5 P7 P14 P7 VGluT2 P14 KCC2 P7 KCC2 2 KCC2 mRNA GABA KCC2
117 185 P NMJ NMJ d NMJ NMJ P Hh Hh Hh SC Hh SC Hh SC Hh P neuroligin 3 neuroligin neurexin Neuroligin Neuroligin family neuroligin neuroligin 1EGFP dsRed2 neuroligin1 Neuroligin1 neuroligin1 neuroligin P 1 2 2 2 3 2 1 4 2 3 ABCD ABCD P 1 1 1 1 2 2 2 2 1 3 2 4 3 22 74 4 4 2 1992IX1 0.8% P 1 1 1,2 1 2 2 2 1 2 Gi F O Tr 3 Nf Gi 2 L5/S1 S1/S2 S1/S2 S2/S2 S1/S1 S2/S2 Gi S1/S2 S2/S2 S2/S3 1Gi2 4 L5/S1 S1/S2 1 Nf L4L4 3 Tr>F>O L4 Tr S1/S2 S2/S2 2 Nf L43 F>Tr>O S1/S1 S2/S2 1 Nf L4F>O>Tr 2Gi1 5 S1/S2 1 L3 Tr Nf L3+L4 S2/S2 2 Nf L4F>Tr>O 1 F>O>Tr 1 S2/S3 2 L4 L5 F, O, Tr 3 Nf L4+L5 Gi
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117 123 P SA 1 2 1 2 Glial
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117 127 P cFos 1 2 1 1
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