Lrp4 in astrocytes modulates glutamatergic transmission

Xiang Dong Sun, Lei Li, Fang Liu, Zhi Hui Huang, Jonathan C. Bean, Hui Feng Jiao, Arnab Barik, Seon Myung Kim, Haitao Wu, Chengyong Shen, Yun Tian, Thiri W. Lin, Ryan Bates, Anupama Sathyamurthy, Yong Jun Chen, Dong Min Yin, Lei Xiong, Hui Ping Lin, Jin Xia Hu, Bao Ming LiTian Ming Gao, Wen Cheng Xiong, Lin Mei

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Neurotransmission requires precise control of neurotransmitter release from axon terminals. This process is regulated by glial cells; however, the underlying mechanisms are not fully understood. We found that glutamate release in the brain was impaired in mice lacking low-density lipoprotein receptor-related protein 4 (Lrp4), a protein that is critical for neuromuscular junction formation. Electrophysiological studies revealed compromised release probability in astrocyte-specific Lrp4 knockout mice. Lrp4 mutant astrocytes suppressed glutamatergic transmission by enhancing the release of ATP, whose level was elevated in the hippocampus of Lrp4 mutant mice. Consequently, the mutant mice were impaired in locomotor activity and spatial memory and were resistant to seizure induction. These impairments could be ameliorated by blocking the adenosine A1 receptor. The results reveal a critical role for Lrp4, in response to agrin, in modulating astrocytic ATP release and synaptic transmission. Our findings provide insight into the interaction between neurons and astrocytes for synaptic homeostasis and/or plasticity.

Original languageEnglish (US)
Pages (from-to)1010-1018
Number of pages9
JournalNature Neuroscience
Volume19
Issue number8
DOIs
StatePublished - Aug 1 2016

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Lipoprotein Receptors
Astrocytes
Mutant Proteins
Synaptic Transmission
Proteins
Adenosine Triphosphate
Agrin
Adenosine A1 Receptors
Neuromuscular Junction
Presynaptic Terminals
Locomotion
Knockout Mice
Neuroglia
Neurotransmitter Agents
Glutamic Acid
Hippocampus
Seizures
Homeostasis
Neurons
Brain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Sun, X. D., Li, L., Liu, F., Huang, Z. H., Bean, J. C., Jiao, H. F., ... Mei, L. (2016). Lrp4 in astrocytes modulates glutamatergic transmission. Nature Neuroscience, 19(8), 1010-1018. https://doi.org/10.1038/nn.4326

Lrp4 in astrocytes modulates glutamatergic transmission. / Sun, Xiang Dong; Li, Lei; Liu, Fang; Huang, Zhi Hui; Bean, Jonathan C.; Jiao, Hui Feng; Barik, Arnab; Kim, Seon Myung; Wu, Haitao; Shen, Chengyong; Tian, Yun; Lin, Thiri W.; Bates, Ryan; Sathyamurthy, Anupama; Chen, Yong Jun; Yin, Dong Min; Xiong, Lei; Lin, Hui Ping; Hu, Jin Xia; Li, Bao Ming; Gao, Tian Ming; Xiong, Wen Cheng; Mei, Lin.

In: Nature Neuroscience, Vol. 19, No. 8, 01.08.2016, p. 1010-1018.

Research output: Contribution to journalArticle

Sun, XD, Li, L, Liu, F, Huang, ZH, Bean, JC, Jiao, HF, Barik, A, Kim, SM, Wu, H, Shen, C, Tian, Y, Lin, TW, Bates, R, Sathyamurthy, A, Chen, YJ, Yin, DM, Xiong, L, Lin, HP, Hu, JX, Li, BM, Gao, TM, Xiong, WC & Mei, L 2016, 'Lrp4 in astrocytes modulates glutamatergic transmission', Nature Neuroscience, vol. 19, no. 8, pp. 1010-1018. https://doi.org/10.1038/nn.4326
Sun XD, Li L, Liu F, Huang ZH, Bean JC, Jiao HF et al. Lrp4 in astrocytes modulates glutamatergic transmission. Nature Neuroscience. 2016 Aug 1;19(8):1010-1018. https://doi.org/10.1038/nn.4326
Sun, Xiang Dong ; Li, Lei ; Liu, Fang ; Huang, Zhi Hui ; Bean, Jonathan C. ; Jiao, Hui Feng ; Barik, Arnab ; Kim, Seon Myung ; Wu, Haitao ; Shen, Chengyong ; Tian, Yun ; Lin, Thiri W. ; Bates, Ryan ; Sathyamurthy, Anupama ; Chen, Yong Jun ; Yin, Dong Min ; Xiong, Lei ; Lin, Hui Ping ; Hu, Jin Xia ; Li, Bao Ming ; Gao, Tian Ming ; Xiong, Wen Cheng ; Mei, Lin. / Lrp4 in astrocytes modulates glutamatergic transmission. In: Nature Neuroscience. 2016 ; Vol. 19, No. 8. pp. 1010-1018.
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