Defect in Synaptic Vesicle Precursor Transport and Neuronal Cell Death in KIF1A Motor Protein-deficient Mice

Yonekawa, Yoshiaki; Harada, Akihiro; Okada, Yasushi; Funakoshi, Takeshi; Kanai, Yoshimitsu; Takei, Yosuke; Terada, Sumio; Noda, Tetsuo; Hirokawa, Nobutaka

doi:https://doi.org/10.1083/jcb.141.2.431

Defect in Synaptic Vesicle Precursor Transport and Neuronal Cell Death in KIF1A Motor Protein-deficient Mice

Yonekawa, Yoshiaki; Harada, Akihiro; Okada, Yasushi et al.

Journal of Cell Biology, 1998, 141(2), 431-441

Number of Access:1,038（2025-07-27 23:20 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/23080

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Title	Defect in Synaptic Vesicle Precursor Transport and Neuronal Cell Death in KIF1A Motor Protein-deficient Mice
Creator	CreatorName Yonekawa, Yoshiaki
	NRID 1000040251441 1000040251441 researchmap permalink aharada aharada Scopus Author ID 7202253419 7202253419 CreatorName Harada, Akihiro
	NRID 1000050272430 1000050272430 CreatorName Okada, Yasushi
	CreatorName Funakoshi, Takeshi
	NRID 1000080214427 1000080214427 CreatorName Kanai, Yoshimitsu
	NRID 1000020272487 1000020272487 CreatorName Takei, Yosuke
	NRID 1000000262022 1000000262022 CreatorName Terada, Sumio
	NRID 1000010183550 1000010183550 CreatorName Noda, Tetsuo
	NRID 1000020010085 1000020010085 CreatorName Hirokawa, Nobutaka
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.
Publisher	The Rockefeller University Press
Source Title	Journal of Cell Biology
Volume (Issue)	141(2)
Page	431-441
Date of Issued	1998-04-20
Language	English
Handle URL	https://hdl.handle.net/11094/23080
PISSN	00219525
NCID	AA00694812
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1083/jcb.141.2.431
Access Rights	open access
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Journal of Cell Biology. 1998, 141(2), p. 431-441
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	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	1998-04-20
DC.identifier	https://doi.org/10.1083/jcb.141.2.431
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.
DC.format	23080
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	English
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_doi	https://doi.org/10.1083/jcb.141.2.431
citation_public_url	https://hdl.handle.net/11094/23080

Defect in Synaptic Vesicle Precursor Transport and Neuronal Cell Death in KIF1A Motor Protein-deficient Mice

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