Zinc transporter ZnT-3 regulates presynaptic Erk1/2 signaling and hippocampus-dependent memory
被引:142
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作者:
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Sindreu, Carlos
[2
]
Palmiter, Richard D.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Washington, Dept Biochem, Seattle, WA 98195 USA
Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USAUniv Washington, Dept Biochem, Seattle, WA 98195 USA
Palmiter, Richard D.
[1
,3
]
Storm, Daniel R.
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机构:
Univ Washington, Dept Pharmacol, Seattle, WA 98195 USAUniv Washington, Dept Biochem, Seattle, WA 98195 USA
Storm, Daniel R.
[2
]
机构:
[1] Univ Washington, Dept Biochem, Seattle, WA 98195 USA
[2] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA
[3] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA
signal transduction;
synaptic zinc;
CA3;
cognition;
SYNAPTICALLY RELEASED ZINC;
LONG-TERM POTENTIATION;
SYNAPSIN-I;
MAP KINASE;
MOSSY;
MICE;
ACTIVATION;
INHIBITION;
RECEPTORS;
VESICLES;
D O I:
10.1073/pnas.1019166108
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:
The physiological role of vesicular zinc at central glutamatergic synapses remains poorly understood. Here we show that mice lacking the synapse-specific vesicular zinc transporter ZnT3 (ZnT3KO mice) have reduced activation of the Erk1/2 MAPK in hippocampal mossy fiber terminals, disinhibition of zinc-sensitive MAPK tyrosine phosphatase activity, and impaired MAPK signaling during hippocampus-dependent learning. Activity-dependent exocytosis is required for the effect of zinc on presynaptic MAPK and phosphatase activity. ZnT3KO mice have complete deficits in contextual discrimination and spatial working memory. Local blockade of zinc or MAPK in the mossy fiber pathway of wild-type mice impairs contextual discrimination. We conclude that ZnT3 is important for zinc homeostasis modulating presynaptic MAPK signaling and is required for hippocampus-dependent memory.
机构:
Univ Calif San Francisco, Dept Surg, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA
Capital Univ Med Sci, Beijing Chao Yang Hosp, Dept Thorac Surg, Beijing, Peoples R ChinaUniv Calif San Francisco, Dept Surg, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA
You, Bin
Yang, Yi-Lin
论文数: 0引用数: 0
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Univ Calif San Francisco, Dept Surg, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Surg, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA
Yang, Yi-Lin
Xu, Zhidong
论文数: 0引用数: 0
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Univ Calif San Francisco, Dept Surg, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Surg, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA
Xu, Zhidong
Dai, Yuyuan
论文数: 0引用数: 0
h-index: 0
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Univ Calif San Francisco, Dept Surg, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Surg, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA
Dai, Yuyuan
Liu, Shu
论文数: 0引用数: 0
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Univ Calif San Francisco, Dept Surg, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Surg, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA
Liu, Shu
Mao, Jian-Hua
论文数: 0引用数: 0
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Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Life Sci Div, Berkeley, CA 94720 USAUniv Calif San Francisco, Dept Surg, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA
Mao, Jian-Hua
Tetsu, Osamu
论文数: 0引用数: 0
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Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, San Francisco, CA USAUniv Calif San Francisco, Dept Surg, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA
Tetsu, Osamu
Li, Hui
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Capital Univ Med Sci, Beijing Chao Yang Hosp, Dept Thorac Surg, Beijing, Peoples R ChinaUniv Calif San Francisco, Dept Surg, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA
Li, Hui
Jablons, David M.
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h-index: 0
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Univ Calif San Francisco, Dept Surg, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Surg, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA
Jablons, David M.
You, Liang
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Dept Surg, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Surg, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA
机构:
Emory Univ, Div Endocrinol, Dept Med, 101 Woodruff Circle,1026 WMRB, Atlanta, GA 30322 USA
Seoul Natl Univ, Bundang Hosp, Dept Radiol, Seungnam 13620, South Korea
IMGT Co Ltd, Seungnam 13605, South KoreaVet Affairs Med Ctr, Atlanta Dept, Decatur, GA 30033 USA
Ha, Shin-Woo
Park, Jonathan
论文数: 0引用数: 0
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机构:
Emory Univ, Div Endocrinol, Dept Med, 101 Woodruff Circle,1026 WMRB, Atlanta, GA 30322 USAVet Affairs Med Ctr, Atlanta Dept, Decatur, GA 30033 USA
Park, Jonathan
Habib, Mark M.
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机构:
Vet Affairs Med Ctr, Atlanta Dept, Decatur, GA 30033 USAVet Affairs Med Ctr, Atlanta Dept, Decatur, GA 30033 USA
Habib, Mark M.
Beck, George R., Jr.
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机构:
Vet Affairs Med Ctr, Atlanta Dept, Decatur, GA 30033 USA
Emory Univ, Div Endocrinol, Dept Med, 101 Woodruff Circle,1026 WMRB, Atlanta, GA 30322 USA
Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA 30322 USAVet Affairs Med Ctr, Atlanta Dept, Decatur, GA 30033 USA