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Myosin Vb Mobilizes Recycling Endosomes and AMPA Receptors for Postsynaptic Plasticity
被引:380
作者:
Wang, Zhiping
[1
,2
]
Edwards, Jeffrey G.
[3
]
Riley, Nathan
[3
]
Provance, D. William, Jr.
[4
]
Karcher, Ryan
[4
]
Li, Xiang-dong
[5
]
Davison, Ian G.
[1
,2
]
Ikebe, Mitsuo
[5
]
Mercer, John A.
[4
]
Kauer, Julie A.
[3
]
Ehlers, Michael D.
[1
,2
]
机构:
[1] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA
[2] Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA
[3] Brown Univ, Dept Mol Pharmacol Physiol & Biotechnol, Providence, RI 02912 USA
[4] McLaughlin Res Inst, Great Falls, MT 59405 USA
[5] Univ Massachusetts, Sch Med, Dept Physiol, Worcester, MA 01655 USA
来源:
关键词:
D O I:
10.1016/j.cell.2008.09.057
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Learning-related plasticity at excitatory synapses in the mammalian brain requires the trafficking of AMPA receptors and the growth of dendritic spines. However, the mechanisms that couple plasticity stimuli to the trafficking of postsynaptic cargo are poorly understood. Here we demonstrate that myosin Vb (MyoVb), a Ca2+-sensitive motor, conducts spine trafficking during long-term potentiation (LTP) of synaptic strength. Upon activation of NMDA receptors and corresponding Ca2+ influx, MyoVb associates with recycling endosomes (REs), triggering rapid spine recruitment of endosomes and local exocytosis in spines. Disruption of MyoVb or its interaction with the RE adaptor Rab11-FIP2 abolishes LTP-induced exocytosis from REs and prevents both AMPA receptor insertion and spine growth. Furthermore, induction of tight binding of MyoVb to actin using an acute chemical genetic strategy eradicates LTP in hippocampal slices. Thus, Ca2+-activated MyoVb captures and mobilizes REs for AMPA receptor insertion and spine growth, providing a mechanistic link between the induction and expression of postsynaptic plasticity.
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页码:535 / 548
页数:14
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