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184<br />
117 <br />
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2008 <br />
FA 0.1 ppm <br />
FA <br />
FA <br />
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20 <br />
FA <br />
FA <br />
FA B <br />
0.1 ppm <br />
B FA <br />
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FA 0.1 ppm <br />
FA 0.1 ppm <br />
FA <br />
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PF <br />
PF Cholera toxin b subunitCTb<br />
CTb cFos <br />
mapping CTb <br />
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CA1<br />
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CTb cFos <br />
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Tubulin polyglutamylation regulates cytoskeletal distribution in brain<br />
Kenji Ohata 1 , Yoshiyuki Konishi 2 , Reiko Tsuchiya 3 , Koji Ikegami 1 ,<br />
Mitsutoshi Setou 1<br />
1<br />
Dept. of Cell Biology and Anatomy, Hamamatsu Univ. Sch. of Med., 2 Dept. of<br />
Human and artificial intelligent Systems, Univ. of Fukui, 3 MitsubishiKagaku<br />
Institute of Life Sciences<br />
Microtubules form the structural basis of neuronal morphology and partake in<br />
directing intracellular transport. Tubulins, components of microtubules, are known<br />
to be highly polyglutamylated in neurons, and we, along with another group,<br />
have recently shown that a part of tubulin tyrosine ligaselike Ttll proteins<br />
catalyzes polyglutamylation of tubulins though the subsequent function of this<br />
polyglutamylation remains unclear. Present study demonstrates that Ttll1 and Ttll7<br />
play major roles in adding glutamate chain to alpha and beta tubulin respectively<br />
in the brain. Ttll1 or Ttll7 singleknockout mice exhibited only a slight decrease<br />
in total polyglutamylation. To reveal the neuronal polyglutamylation function, we<br />
generated Ttll1Ttll7 doubleknockout mice which showed significant decrease<br />
in neuronal polyglutamylation. Immunohistochemical and electron microscopic<br />
analyses showed fewer neurofilaments in dendrites of cortical neurons in the<br />
doubleknockout mice compared to the wild type, while the neurofilament<br />
distribution in Ttll1 or Ttll7 singleknockout mice was similar to that of the<br />
wild type. These results suggest that polyglutamilation regulates neurofilament<br />
arrangement.<br />
P<br />
KCC <br />
1 2<br />
1<br />
2 <br />
3 KCC2 Cl – <br />
GABA <br />
<br />
KCC2 in situ hybridization <br />
in situ hybridization KCC2<br />
mRNA 5 P5 P7 <br />
P14 <br />
<br />
P7 <br />
VGluT2 <br />
P14 KCC2 <br />
P7 <br />
KCC2 <br />
<br />
2 KCC2 mRNA <br />
GABA <br />
KCC2