English TOP

Address

Sone Laboratory
Department of Biomolecular Science,
Faculty of Science,
Toho University

Miyama2-2-1, Funabashi,
Chiba, 274-8510 Japan

Current Research

We study neurobiology by genetic methods using the fruit fly, Drosophila melanogaster. Our research aims to elucidate the molecular mechanisms that underlie brain functions that control complicated animal behavior and brain dysfunctions such as neurodegenerative diseases.

Regulatory mechanisms of intracellular protein trafficking and their relevance to brain function and dysfunction.

Major parts of synaptic proteins are synthesized in neuronal cell bodies and are then transported to synaptic terminals through axons. We are interested in the role of the regulatory mechanisms of intracellular protein trafficking in the formation of neural circuits and in neurodegeneration.
Our research primarily focuses on two proteins, Hikaru genki (HIG) and Amyloid precursor protein (APP). Although both of these two proteins are synaptic proteins, they are transported to synapses only at specific developmental stages. In insects, neuronal networks of the adult brain are formed at the pupal stage. HIG and APP proteins are transported to synapses at the early pupal stages when the formation of synapses is actively occurring. However, the transportation of HIG and APP is suppressed at later stages. Our goal is to elucidate the mechanisms that control the differential trafficking of these proteins. Additionally, we hope to reveal the significance of this regulation in neural development and neurodegeneration.
APP is a well-known causative protein of Alzheimer's disease, which is a major cause of dementia. We recently succeeded in identifying a novel gene that is required for the synaptic transport of APP. We named this gene yata after a legendary crow that guided an ancient Japanese emperor to his destination. In null mutants of the yata gene, the synaptic transport of APP is impaired and APP accumulates in the endoplasmic reticulum. Intriguingly, null mutants of the yata gene display phenotypes that include signs of neurodegeneration, such as tissue vacuolization, shortened lifespan and brain volume reduction. Knockout mice for the yata ortholog have been reported to display the degeneration of motor neurons, which suggests that yata has an evolutionarily conserved role in the prevention of neurodegeneration. Our aim is to elucidate the mechanisms that cause neurodegeneration in yata mutants and to determine their relevance in Alzheimer's disease.
Reference:
Loss of yata, a novel gene regulating the subcellular localization of APPL, induces deterioration of neural tissues and lifespan shortening.
Masaki Sone, Atsuko Uchida, Ayumi Komatsu, Emiko Suzuki, Ikue Ibuki, Megumi Asada, Hiroki Shiwaku, Takuya Tamura, Mikio Hoshino, Hitoshi Okazawa, Yo-ichi Nabeshima
PLoS One, 4, e4466 (2009).

PubMed

Drosophila models of neurodegenerative diseases.

We study Drosophila models of polyglutamine diseases such as Huntington's disease and Spinocerebellar ataxia type 1 (SCA1).
Reference:
A functional deficiency of TERA/VCP/p97 contributes to impaired DNA repair in multiple polyglutamine diseases.
Kyota Fujita, Yoko Nakamura, Tsutomu Oka, Hikaru Ito, Takuya Tamura, Kazuhiko Tagawa, Toshikazu Sasabe, Asuka Katsuta, Kazumi Motoki, Hiroki Shiwaku, Masaki Sone, Chisato Yoshida, Masahisa Katsuno, Yoshinobu Eishi, Miho Murata, J. Paul Taylor, Erich E. Wanker, Kazuteru Kono, Satoshi Tashiro, Gen Sobue, Albert R. La Spada, Hitoshi Okazawa
Nature Commun., 4, 1816 (2013).

PubMed

Molecular mechanisms that control animal behavior.

We study the Drosophila mutants, still life (sif) and hikaru genki (hig), both of which display sluggishness. sif encodes an activator of the small G-protein, Rac, and is specifically localized in synaptic periactive zones, which are specialized submembranous regions that regulate synaptic development. hig encodes a protein that has an immunoglobulin domain and complement-binding domains and that is secreted to synaptic clefts. We hope to elucidate the mechanisms that underlie the abnormal behavior of these mutants.
References:
Synaptic development is controlled in the periactive zones of Drosophila synapses.
Masaki Sone, Emiko Suzuki, Mikio Hoshino, Dongmei Hou, Hiroshi Kuromi, Masaki Fukata, Shinya Kuroda, Kozo Kaibuchi, Yo-ichi Nabeshima, Chihiro Hama
Development, 127, 4157-4168 (2000).

PubMed

Still life, a protein in synaptic terminals of Drosophila homologous to GDP-GTP exchangers.
Masaki Sone, Mikio Hoshino, Emiko Suzuki, Shinya Kuroda, Kozo Kaibuchi, Hideki Nakagoshi, Kaoru Saigo, Yo-ichi Nabeshima, Chihiro Hama
Science, 275, 543-547 (1997).

PubMed

Publications

Systematic analysis of fly models with multiple drivers reveals different effects for Ataxin-1 and Huntingtin in neuron subtype-specific expression.
Risa Shiraishi, Takuya Tamura, Masaki Sone, Hitoshi Okazawa
PLoS One, 9, e116567 (2014).
Systems biology abalysis of Drosophila in vivo screen data elucidates core networks for DNA damage repair in SCA1.
Sam S Barclay, Takuya Tamura, Hikaru Ito, Kyota Fujita, Kazuhiko Tagawa, Teppei Shimamura, Asuka Katsuta, Hiroki Shiwaku, Masaki Sone, Seiya Imoto, Satoru Miyano, Hitoshi Okazawa
Hum. Mol. Genet., 23, 1345-1364 (2014).
A functional deficiency of TERA/VCP/p97 contributes to impaired DNA repair in multiple polyglutamine diseases.
Kyota Fujita, Yoko Nakamura, Tsutomu Oka, Hikaru Ito, Takuya Tamura, Kazuhiko Tagawa, Toshikazu Sasabe, Asuka Katsuta, Kazumi Motoki, Hiroki Shiwaku, Masaki Sone, Chisato Yoshida, Masahisa Katsuno, Yoshinobu Eishi, Miho Murata, J. Paul Taylor, Erich E. Wanker, Kazuteru Kono, Satoshi Tashiro, Gen Sobue, Albert R. La Spada, Hitoshi Okazawa
Nature Commun., 4, 1816 (2013).

PubMed

A restricted level of PQBP1 is needed for the best longevity of Drosophila.
Takuya Tamura, Masaki Sone, Yoko Nakamura, Teppei Shimamura, Seiya Imoto, Satoru Miyano, Hitoshi Okazawa
Neurobiol. Aging, 34, 356.e11-356.e20 (2013).

PubMed

Ku70 alleviates neurodegeneration in Drosophila models of Huntington's disease.
Takuya Tamura, Masaki Sone, Takeshi Iwatsubo, Kazuhiko Tagawa, Erich E. Wanker, Hitoshi Okazawa
PLoS One, 6, e27408 (2011). 

PubMed

Drosophila PQBP1 regulates learning acquisition at projection neurons in aversive olfactory conditioning.
Takuya Tamura, Daisuke Horiuchi, Yi-Chung Chen, Masaki Sone, Tomoyuki Miyashita, Minoru Saitoe, Natsue Yoshimura, Ann-Shyn Chiang, Hitoshi Okazawa
J. Neurosci., 30, 14091-14101 (2010). 

PubMed

Suppression of the novel ER protein Maxer by mutant ataxin-1 in Bergman glia contributes to non-cell-autonomous toxicity.
Hiroki Shiwaku, Natsue Yoshimura, Takuya Tamura, Masaki Sone, Soichi Ogishima, Kei Watase, Kazuhiko Tagawa, Hitoshi Okazawa
EMBO J., 29, 2446-2460 (2010). 

PubMed

Mutant huntingtin impairs Ku70-mediated DNA repair.
Yasushi Enokido, Takuya Tamura, Hikaru Ito, Anup Arumughan, Akihiko Komuro, Hiroki Shiwaku, Masaki Sone, Raphaele Foulle, Hirohide Sawada, Hiroshi Ishiguro, Tetsuya Ono, Miho Murata, Ichiro Kanazawa, Nikolai Tomilin, Kazuhiko Tagawa, Erich E Wanker, Hitoshi Okazawa
J. Cell Biol., 189, 425-443 (2010). 

PubMed

Selected Publications of Masaki Sone, Ph.D. before 2009

Loss of yata, a novel gene regulating the subcellular localization of APPL, induces deterioration of neural tissues and lifespan shortening.
Masaki Sone^, Atsuko Uchida, Ayumi Komatsu, Emiko Suzuki, Ikue Ibuki, Megumi Asada, Hiroki Shiwaku, Takuya Tamura, Mikio Hoshino, Hitoshi Okazawa, Yo-ichi Nabeshima
PLoS One, 4, e4466 (2009). (^: corresponding author)

PubMed

Glial cell lineage expression of mutant ataxin-1 and huntingtin induces developmental and late-onset neuronal pathologies in Drosophila models.
Takuya Tamura, Masaki Sone, Mayumi Yamashita, Erich E. Wanker, Hitoshi Okazawa
PLoS One, 4, e4262 (2009). 

PubMed

Ptf1a, a bHLH transcriptional gene, defines GABAergic neuronal fates in cerebellum.
Mikio Hoshino, Shoko Nakamura, Kiyoshi Mori, Takeshi Kawauchi, Mami Terao, Yoshiaki V. Nishimura, Akihisa Fukuda, Toshimitsu Fuse, Naoki Matsuo, Masaki Sone, Masahiko Watanabe, Haruhiko Bito, Toshio Terashima, Christopher V. E. Wright, Yoshiya Kawaguchi, Kazuwa Nakao, Yo-ichi Nabeshima
Neuron, 47, 201-213 (2005).

PubMed

Involvement of a Rac activator, P-Rex1, in neurotrophin-derived signaling and neuronal migration.
Masato Yoshizawa, Masaki Sone&, Takeshi Kawauchi&, Yoshiaki V. Nishimura, Mami Terao, Kaori Chihama, Yo-ichi Nabeshima, Mikio Hoshino
J. Neurosci., 25, 4406-4419 (2005)
(&: equal contribution).

PubMed

Dynamic and coordinated expression profile of Dbl-family guanine nucleotide exchange factors in the developing mouse brain.
Masato Yoshizawa, Masaki Sone, Naoki Matsuo, Takahiro Nagase, Osamu Ohara,
Yo-ichi Nabeshima, Mikio Hoshino
Gene Expr. Pat., 3, 375-381 (2003).

PubMed

Expression of stef, an activator of Rac1, correlates with the stages of neuronal morphological development in the mouse brain.
Masato Yoshizawa, Mikio Hoshino, Masaki Sone, Yo-ichi Nabeshima
Mech. Dev., 113, 65-68 (2002).

PubMed

Synaptic development is controlled in the periactive zones of Drosophila synapses.
Masaki Sone, Emiko Suzuki, Mikio Hoshino, Dongmei Hou, Hiroshi Kuromi, Masaki Fukata, Shinya Kuroda, Kozo Kaibuchi, Yo-ichi Nabeshima, Chihiro Hama
Development, 127, 4157-4168 (2000).

PubMed

The Drosophila Trio plays an essential role in patterning of axons by regulating their directional extension.
Takeshi Awasaki, Mai Saito, Masaki Sone, Emiko Suzuki, Ryoko Sakai, Kei Ito, Chihiro Hama
Neuron, 26, 119-131 (2000).

PubMed

Gal4/USA-WGA system as a powerful tool for tracing Drosophila transsynaptic neural pathways.
Katsuhiko Tabuchi, Kazunobu Sawamoto, Emiko Suzuki, Koichi Ozaki, Masaki Sone, Chihiro Hama, Takako Tanifuji-Morimoto, Yoshihiro Yuasa, Yoshihiro Yoshihara, Akinao Nose, Hideyuki Okano
J. Neurosci. Res., 59, 94-99 (2000). 

PubMed

Identification of the stef gene that encodes a novel guanine-nucleotide exchange factor specific for Rac1.
Mikio Hoshino, Masaki Sone, Masaki Fukata, Shinya Kuroda, Kozo Kaibuchi, Yo-ichi Nabeshima, Chihiro Hama
J. Biol. Chem., 274, 17837-17844 (1999).

PubMed

Neural expression of Hikaru genki protein during embryonic and larval development of Drosophila melanogaster.
Mikio Hoshino, Emiko Suzuki, Tadashi Miyake, Masaki Sone, Akira Komatsu, Yo-ichi Nabeshima, Chihiro Hama
Dev. Genes Evol., 209, 1-9 (1999).

PubMed

Still life, a protein in synaptic terminals of Drosophila homologous to GDP-GTP exchangers.
Masaki Sone, Mikio Hoshino, Emiko Suzuki, Shinya Kuroda, Kozo Kaibuchi, Hideki Nakagoshi, Kaoru Saigo, Yo-ichi Nabeshima, Chihiro Hama
Science, 275, 543-547 (1997).

PubMed

Mechanism of induction of Bar-like eye malformation by transient overexpression of Bar homeobox genes in Drosophila melanogaster.
Masaki Sone&, Tetsuya Kojima&, Tatsuo Michiue&, Kaoru Saigo
Genetica, 88, 85-91 (1993) (& : equal contribution). 

PubMed

Identification of a different-type homeobox gene BarHI, possibly causing Bar (B) and Om(1D) mutations in Drosophila.
Tetsuya Kojima, Satoshi Ishimaru, Shin-ichi Higashijima, Eiji Takayama, Hiroshi Akimaru, Masaki Sone, Yasufumi Emori, Kaoru Saigo
Proc. Natl. Acad. Sci. USA, 88, 4343-4347 (1991). 

PubMed

Information

2013/08/19 English page renew!