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
Y1 - 2013/12
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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U2 - 10.1002/jnr.23273
DO - 10.1002/jnr.23273
M3 - Article
C2 - 24105954
AN - SCOPUS:84886639030
SN - 0360-4012
VL - 91
SP - 1525
EP - 1532
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
IS - 12
ER -