SHATI/NAT8L regulates neurite outgrowth via microtubule stabilization

Kazuya Toriumi, Miki Ikami, Mizuki Kondo, Akihiro Mouri, Takenao Koseki, Daisuke Ibi, Yoko Furukawa-Hibi, Taku Nagai, Takayoshi Mamiya, Atsumi Nitta, Kiyofumi Yamada, Toshitaka Nabeshima

Research output: Contribution to journalArticle

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Abstract

We previously identified a new molecule, "SHATI/NAT8L," which has an inhibitory effect on methamphetamine (METH)-induced hyperlocomotion, sensitization, and conditioned place preference. Nevertheless, the extent of SHATI localization and its functions are only partially understood. In this study, we used the FLAG-tag method to investigate SHATI localization. We found that SHATI was localized to microtubules when expressed in COS7 cells and cortical primary neurons. This distribution of SHATI was less apparent after cells were treated with colchicine, a tubulin polymerization inhibitor that disrupts the microtubule structure. This finding suggests that SHATI is associated with microtubule structure. Interestingly, overexpression of SHATI in COS7 cells could attenuate the colchicine-induced decrease in acetylated microtubules, indicating that SHATI plays a role in stabilizing microtubules. Furthermore, we showed that Shati deletion impaired neurite elongation. In cortical primary neurons, neurite length and complexity in Shati-knockout (KO) mice were significantly decreased. In pyramidal neurons in the prefrontal cortex, dendrite length and complexity were also significantly decreased in Shati-KO mice compared with wild-type mice. These results suggest a novel function for SHATI, which may be a new member of the microtubule-associated protein family.

Original languageEnglish
Pages (from-to)1525-1532
Number of pages8
JournalJournal of Neuroscience Research
Volume91
Issue number12
DOIs
Publication statusPublished - 01-12-2013
Externally publishedYes

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Microtubules
Colchicine
Neurites
Knockout Mice
Tubulin Modulators
Neurons
Microtubule-Associated Proteins
Methamphetamine
Pyramidal Cells
Dendrites
Prefrontal Cortex
Neuronal Outgrowth

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

Cite this

Toriumi, Kazuya ; Ikami, Miki ; Kondo, Mizuki ; Mouri, Akihiro ; Koseki, Takenao ; Ibi, Daisuke ; Furukawa-Hibi, Yoko ; Nagai, Taku ; Mamiya, Takayoshi ; Nitta, Atsumi ; Yamada, Kiyofumi ; Nabeshima, Toshitaka. / SHATI/NAT8L regulates neurite outgrowth via microtubule stabilization. In: Journal of Neuroscience Research. 2013 ; Vol. 91, No. 12. pp. 1525-1532.
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Toriumi, K, Ikami, M, Kondo, M, Mouri, A, Koseki, T, Ibi, D, Furukawa-Hibi, Y, Nagai, T, Mamiya, T, Nitta, A, Yamada, K & Nabeshima, T 2013, 'SHATI/NAT8L regulates neurite outgrowth via microtubule stabilization', Journal of Neuroscience Research, vol. 91, no. 12, pp. 1525-1532. https://doi.org/10.1002/jnr.23273

SHATI/NAT8L regulates neurite outgrowth via microtubule stabilization. / Toriumi, Kazuya; Ikami, Miki; Kondo, Mizuki; Mouri, Akihiro; Koseki, Takenao; Ibi, Daisuke; Furukawa-Hibi, Yoko; Nagai, Taku; Mamiya, Takayoshi; Nitta, Atsumi; Yamada, Kiyofumi; Nabeshima, Toshitaka.

In: Journal of Neuroscience Research, Vol. 91, No. 12, 01.12.2013, p. 1525-1532.

Research output: Contribution to journalArticle

TY - JOUR

T1 - SHATI/NAT8L regulates neurite outgrowth via microtubule stabilization

AU - Toriumi, Kazuya

AU - Ikami, Miki

AU - Kondo, Mizuki

AU - Mouri, Akihiro

AU - Koseki, Takenao

AU - Ibi, Daisuke

AU - Furukawa-Hibi, Yoko

AU - Nagai, Taku

AU - Mamiya, Takayoshi

AU - Nitta, Atsumi

AU - Yamada, Kiyofumi

AU - Nabeshima, Toshitaka

PY - 2013/12/1

Y1 - 2013/12/1

N2 - We previously identified a new molecule, "SHATI/NAT8L," which has an inhibitory effect on methamphetamine (METH)-induced hyperlocomotion, sensitization, and conditioned place preference. Nevertheless, the extent of SHATI localization and its functions are only partially understood. In this study, we used the FLAG-tag method to investigate SHATI localization. We found that SHATI was localized to microtubules when expressed in COS7 cells and cortical primary neurons. This distribution of SHATI was less apparent after cells were treated with colchicine, a tubulin polymerization inhibitor that disrupts the microtubule structure. This finding suggests that SHATI is associated with microtubule structure. Interestingly, overexpression of SHATI in COS7 cells could attenuate the colchicine-induced decrease in acetylated microtubules, indicating that SHATI plays a role in stabilizing microtubules. Furthermore, we showed that Shati deletion impaired neurite elongation. In cortical primary neurons, neurite length and complexity in Shati-knockout (KO) mice were significantly decreased. In pyramidal neurons in the prefrontal cortex, dendrite length and complexity were also significantly decreased in Shati-KO mice compared with wild-type mice. These results suggest a novel function for SHATI, which may be a new member of the microtubule-associated protein family.

AB - We previously identified a new molecule, "SHATI/NAT8L," which has an inhibitory effect on methamphetamine (METH)-induced hyperlocomotion, sensitization, and conditioned place preference. Nevertheless, the extent of SHATI localization and its functions are only partially understood. In this study, we used the FLAG-tag method to investigate SHATI localization. We found that SHATI was localized to microtubules when expressed in COS7 cells and cortical primary neurons. This distribution of SHATI was less apparent after cells were treated with colchicine, a tubulin polymerization inhibitor that disrupts the microtubule structure. This finding suggests that SHATI is associated with microtubule structure. Interestingly, overexpression of SHATI in COS7 cells could attenuate the colchicine-induced decrease in acetylated microtubules, indicating that SHATI plays a role in stabilizing microtubules. Furthermore, we showed that Shati deletion impaired neurite elongation. In cortical primary neurons, neurite length and complexity in Shati-knockout (KO) mice were significantly decreased. In pyramidal neurons in the prefrontal cortex, dendrite length and complexity were also significantly decreased in Shati-KO mice compared with wild-type mice. These results suggest a novel function for SHATI, which may be a new member of the microtubule-associated protein family.

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