A synthetic synaptic organizer protein restores glutamatergic neuronal circuits

被引：82

作者：

Suzuki, Kunimichi ^{[1
,9
]}

Elegheert, Jonathan ^{[2
,10
]}

Song, Inseon ^{[3
]}

Sasakura, Hiroyuki ^{[4
]}

Senkov, Oleg ^{[3
]}

Matsuda, Keiko ^{[1
]}

Kakegawa, Wataru ^{[1
]}

Clayton, Amber J. ^{[2
,11
]}

Chang, Veronica T. ^{[2
,5
]}

Ferrer-Ferrer, Maura ^{[3
]}

Miura, Eriko ^{[1
]}

Kaushik, Rahul ^{[3
,6
]}

Ikeno, Masashi ^{[4
]}

Morioka, Yuki ^{[4
]}

Takeuchi, Yuka ^{[4
]}

Shimada, Tatsuya ^{[1
]}

Otsuka, Shintaro ^{[1
]}

Stoyanov, Stoyan ^{[3
]}

Watanabe, Masahiko ^{[7
]}

Takeuchi, Kosei ^{[4
]}

Dityatev, Alexander ^{[3
,6
,8
]}

Aricescu, A. Radu ^{[2
,5
]}

Yuzaki, Michisuke ^{[1
]}

机构：

[1] Keio Univ, Dept Physiol, Sch Med, Tokyo 1608582, Japan

[2] Univ Oxford, Div Struct Biol, Oxford OX3 7BN, England

[3] German Ctr Neurodegenerat Dis DZNE, Mol Neuroplast, D-39120 Magdeburg, Germany

[4] Aichi Med Univ, Dept Med Cell Biol, Sch Med, Nagakute, Aichi, Japan

[5] MRC Lab Mol Biol, Neurobiol Div, Cambridge CB2 0QH, England

[6] Ctr Behav Brain Sci CBBS, D-39106 Magdeburg, Germany

[7] Hokkaido Univ, Grad Sch Med, Dept Anat, Sapporo, Hokkaido 0608638, Japan

[8] Otto von Guericke Univ, Fac Med, D-39120 Magdeburg, Germany

[9] MRC Lab Mol Biol, Div Neurobiol, Cambridge CB2 0QH, England

[10] UB, Interdisciplinary Inst Neurosci IINS, CNRS, UMR5297, F-33076 Bordeaux, France

[11] Adaptimmune, 60 Jubilee Ave,Milton Pk, Abingdon OX14 4RX, Oxon, England

来源：

SCIENCE | 2020年 / 369卷 / 6507期

基金：

英国医学研究理事会; 欧盟第七框架计划; 日本学术振兴会; 欧洲研究理事会;

关键词：

LONG-TERM POTENTIATION; SPINAL-CORD; EXCITATORY SYNAPSES; FUNCTIONAL RECOVERY; AMPA RECEPTORS; INTEGRATION; PLASTICITY; CBLN1; CEREBELLINS; SPECIFICITY;

D O I：

10.1126/science.abb4853

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：

Neuronal synapses undergo structural and functional changes throughout life, which are essential for nervous system physiology. However, these changes may also perturb the excitatory-inhibitory neurotransmission balance and trigger neuropsychiatric and neurological disorders. Molecular tools to restore this balance are highly desirable. Here, we designed and characterized CPTX, a synthetic synaptic organizer combining structural elements from cerebellin-1 and neuronal pentraxin-1. CPTX can interact with presynaptic neurexins and postsynaptic AMPA-type ionotropic glutamate receptors and induced the formation of excitatory synapses both in vitro and in vivo. CPTX restored synaptic functions, motor coordination, spatial and contextual memories, and locomotion in mouse models for cerebellar ataxia, Alzheimer's disease, and spinal cord injury, respectively. Thus, CPTX represents a prototype for structure-guided biologics that can efficiently repair or remodel neuronal circuits.

引用

页码：1074 / +

页数：51

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