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jcb_141_2_431
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論文情報
タイトル
Defect in Synaptic Vesicle Precursor Transport and Neuronal Cell Death in KIF1A Motor Protein-deficient Mice
著者
Yonekawa, Yoshiaki
Yonekawa, Yoshiaki
Harada, Akihiro
Harada, Akihiro
Okada, Yasushi
Okada, Yasushi
Funakoshi, Takeshi
Funakoshi, Takeshi
Kanai, Yoshimitsu
Kanai, Yoshimitsu
Takei, Yosuke
Takei, Yosuke
Terada, Sumio
Terada, Sumio
Noda, Tetsuo
Noda, Tetsuo
Hirokawa, Nobutaka
Hirokawa, Nobutaka
抄録
The nerve axon is a good model system for studying the molecular mechanism of organelle transport in cells. Recently, the new kinesin superfamily proteins (KIFs) have been identified as candidate motor proteins involved in organelle transport. Among them KIF1A, a murine homologue of unc-104 gene of Caenorhabditis elegans , is a unique monomeric neuronspecific microtubule plus end–directed motor and has been proposed as a transporter of synaptic vesicle precursors (Okada, Y., H. Yamazaki, Y. Sekine-Aizawa, and N. Hirokawa. 1995. Cell. 81:769–780). To elucidate the function of KIF1A in vivo, we disrupted the KIF1A gene in mice. KIF1A mutants died mostly within a day after birth showing motor and sensory disturbances. In the nervous systems of these mutants, the transport of synaptic vesicle precursors showed a specific and significant decrease. Consequently, synaptic vesicle density decreased dramatically, and clusters of clear small vesicles accumulated in the cell bodies. Furthermore, marked neuronal degeneration and death occurred both in KIF1A mutant mice and in cultures of mutant neurons. The neuronal death in cultures was blocked by coculture with wild-type neurons or exposure to a low concentration of glutamate. These results in cultures suggested that the mutant neurons might not sufficiently receive afferent stimulation, such as neuronal contacts or neurotransmission, resulting in cell death. Thus, our results demonstrate that KIF1A transports a synaptic vesicle precursor and that KIF1A-mediated axonal transport plays a critical role in viability, maintenance, and function of neurons, particularly mature neurons.
公開者
The Rockefeller University Press
掲載誌名
Journal of Cell Biology
巻
141
号
2
開始ページ
431
終了ページ
441
刊行年月
1998-04-20
ISSN
00219525
NCID
AA00694812
DOI (出版社版)
info:doi/10.1083/jcb.141.2.431
URL
http://hdl.handle.net/11094/23080
言語
英語
カテゴリ
学術雑誌論文 Journal Article
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著者版フラグ
publisher
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学術雑誌論文
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dcmi資源タイプ
text
DCTERMS.bibliographicCitation
Journal of Cell Biology.141(2) P.431-P.441
DC.title
Defect in Synaptic Vesicle Precursor Transport and Neuronal Cell Death in KIF1A Motor Protein-deficient Mice
DC.creator
Yonekawa, Yoshiaki
Harada, Akihiro
Okada, Yasushi
Funakoshi, Takeshi
Kanai, Yoshimitsu
Takei, Yosuke
Terada, Sumio
Noda, Tetsuo
Hirokawa, Nobutaka
DC.publisher
The Rockefeller University Press
DC.language" scheme="DCTERMS.RFC1766
英語
DCTERMS.issued" scheme="DCTERMS.W3CDTF
1998-04-20
DC.identifier
info:doi/10.1083/jcb.141.2.431
DC.identifier" scheme="DCTERMS.URI
http://hdl.handle.net/11094/23080
DCTERMS.abstract
The nerve axon is a good model system for studying the molecular mechanism of organelle transport in cells. Recently, the new kinesin superfamily proteins (KIFs) have been identified as candidate motor proteins involved in organelle transport. Among them KIF1A, a murine homologue of unc-104 gene of Caenorhabditis elegans , is a unique monomeric neuronspecific microtubule plus end–directed motor and has been proposed as a transporter of synaptic vesicle precursors (Okada, Y., H. Yamazaki, Y. Sekine-Aizawa, and N. Hirokawa. 1995. Cell. 81:769–780). To elucidate the function of KIF1A in vivo, we disrupted the KIF1A gene in mice. KIF1A mutants died mostly within a day after birth showing motor and sensory disturbances. In the nervous systems of these mutants, the transport of synaptic vesicle precursors showed a specific and significant decrease. Consequently, synaptic vesicle density decreased dramatically, and clusters of clear small vesicles accumulated in the cell bodies. Furthermore, marked neuronal degeneration and death occurred both in KIF1A mutant mice and in cultures of mutant neurons. The neuronal death in cultures was blocked by coculture with wild-type neurons or exposure to a low concentration of glutamate. These results in cultures suggested that the mutant neurons might not sufficiently receive afferent stimulation, such as neuronal contacts or neurotransmission, resulting in cell death. Thus, our results demonstrate that KIF1A transports a synaptic vesicle precursor and that KIF1A-mediated axonal transport plays a critical role in viability, maintenance, and function of neurons, particularly mature neurons.
citation_title
Defect in Synaptic Vesicle Precursor Transport and Neuronal Cell Death in KIF1A Motor Protein-deficient Mice
citation_author
Yonekawa, Yoshiaki
Harada, Akihiro
Okada, Yasushi
Funakoshi, Takeshi
Kanai, Yoshimitsu
Takei, Yosuke
Terada, Sumio
Noda, Tetsuo
Hirokawa, Nobutaka
citation_publisher
The Rockefeller University Press
citation_language
英語
citation_date
1998-04-20
citation_journal_title
Journal of Cell Biology
citation_volume
141
citation_issue
2
citation_firstpage
431
citation_lastpage
441
citation_issn
00219525
citation_doi
info:doi/10.1083/jcb.141.2.431
citation_public_url
http://hdl.handle.net/11094/23080