Alpha-synuclein facilitates to form short unconventional microtubules that have a unique function in the axonal transport

被引：24

作者：

Toba, Shiori ^{[1
]}

Jin, Mingyue ^{[1
]}

Yamada, Masami ^{[1
]}

Kumamoto, Kanako ^{[1
]}

Matsumoto, Sakiko ^{[1
]}

Yasunaga, Takuo ^{[2
,3
,4
]}

Fukunaga, Yuko ^{[5
,6
]}

Miyazawa, Atsuo ^{[5
,6
]}

Fujita, Sakiko ^{[7
]}

Itoh, Kyoko ^{[8
]}

Fushiki, Shinji ^{[8
]}

Kojima, Hiroaki ^{[9
]}

Wanibuchi, Hideki ^{[10
]}

Arai, Yoshiyuki ^{[11
]}

Nagai, Takeharu ^{[11
]}

Hirotsune, Shinji ^{[1
]}

机构：

[1] Osaka City Univ, Grad Sch Med, Dept Genet Dis Res, Asahi Machi 1-4-3 Abeno, Osaka 5458585, Japan

[2] Kyushu Inst Technol, Fac Comp Sci & Syst Engn, Dept Biosci & Bioinformat, Kawazu 680-4, Iizuka, Fukuoka 820850, Japan

[3] JST SENTAN, 4-1-8 Honcho, Kawaguchi, Saitama 3320012, Japan

[4] JST CREST, 4-1-8 Honcho, Kawaguchi, Saitama 3320012, Japan

[5] Univ Hyogo, Grad Sch Life Sci, 3-2-1 Kouto,Kamigori Cho, Kobe, Hyogo 6781297, Japan

[6] Univ Hyogo, Leading Program Ctr, RIKEN, SPring Ctr 8,RSC, 1-1-1 Kouto,Sayo Cho, Kobe, Hyogo 6795148, Japan

[7] Nara Inst Sci & Technol, Grad Sch Mat Sci, 8916-5 Takayama, Nara 6300101, Japan

[8] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Dept Pathol & Appl Neurobiol, Kamigyo Ku, Kajii Cho, Kyoto 6028566, Japan

[9] Natl Inst Informat & Commun Technol, Adv ICT Res Inst, Nishi Ku, 588-2 Iwaoka, Kobe, Hyogo 6512492, Japan

[10] Osaka City Univ, Grad Sch Med, Dept Pathol, Asahi Machi 1-4-3 Abeno, Osaka 5458586, Japan

[11] Osaka Univ, Inst Sci & Ind Res, Dept Biomol Sci & Engn, Mihoga Oka 8-1, Osaka 5670047, Japan

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

基金：

日本学术振兴会;

关键词：

END-DIRECTED TRANSPORT; CYTOPLASMIC DYNEIN; NEURONAL MIGRATION; PROTEIN-TAU; IN-VITRO; KINESIN; BRAIN; POLYMERIZATION; MUTATION; LIS1;

D O I：

10.1038/s41598-017-15575-3

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Although alpha-synuclein (alpha Syn) has been linked to Parkinson's disease (PD), the mechanisms underlying the causative role in PD remain unclear. We previously proposed a model for a transportable microtubule (tMT), in which dynein is anchored to a short tMT by LIS1 followed by the kinesindependent anterograde transport; however the mechanisms that produce tMTs have not been determined. Our in vitro investigations of microtubule (MT) dynamics revealed that alpha Syn facilitates the formation of short MTs and preferentially binds to MTs carrying 14 protofilaments (pfs). Live-cell imaging showed that alpha Syn co-transported with dynein and mobile beta III-tubulin fragments in the anterograde transport. Furthermore, bi-directional axonal transports are severely affected in alpha Syn and gamma Syn depleted dorsal root ganglion neurons. SR-PALM analyses further revealed the fibrous co-localization of alpha Syn, dynein and beta III-tubulin in axons. More importantly, 14-pfs MTs have been found in rat femoral nerve tissue, and they increased approximately 19 fold the control in quantify upon nerve ligation, indicating the unconventional MTs are mobile. Our findings indicate that alpha Syn facilitates to form short, mobile tMTs that play an important role in the axonal transport. This unexpected and intriguing discovery related to axonal transport provides new insight on the pathogenesis of PD.

引用

页数：19