A synthetic synaptic organizer protein restores glutamatergic neuronal circuits.
Science. ; 369(6507): 1052-1053
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Suzuki K(#)(1), Elegheert J(#)(2), Song I(#)(3), Sasakura H(#)(4), Senkov O(3), Matsuda K(1), Kakegawa W(1), Clayton AJ(2), Chang VT(2)(5), Ferrer-Ferrer M(3), Miura E(1), Kaushik R(3)(6), Ikeno M(4), Morioka Y(4), Takeuchi Y(4), Shimada T(1), Otsuka S(1), Stoyanov S(3), Watanabe M(7), Takeuchi K(4), Dityatev A(8)(6)(9), Aricescu AR(10)(5), Yuzaki M(11).
(1)Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan.
(2)Division of Structural Biology, University of Oxford, Oxford OX3 7BN, UK.
(3)Molecular Neuroplasticity, German Center for Neurodegenerative Diseases (DZNE), 39120 Magdeburg, Germany.
(4)Department of Medical Cell Biology, School of Medicine, Aichi Medical University, Aichi, Japan.
(5)Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
(6)Center for Behavioral Brain Sciences (CBBS), 39106 Magdeburg, Germany.
(7)Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
(8)Molecular Neuroplasticity, German Center for Neurodegenerative Diseases (DZNE), 39120 Magdeburg, Germany. .
(9)Medical Faculty, Otto von Guericke University, 39120 Magdeburg, Germany.
(10)Division of Structural Biology, University of Oxford, Oxford OX3 7BN, UK. .
(11)Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan. .
Science. 2020 Aug 28;369(6507):1052-1053.
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.