RT Journal Article
SR Electronic
T1 A synthetic synaptic organizer protein restores glutamatergic neuronal circuits
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.02.27.967836
DO 10.1101/2020.02.27.967836
A1 Kunimichi Suzuki
A1 Jonathan Elegheert
A1 Inseon Song
A1 Hiroyuki Sasakura
A1 Oleg Senkov
A1 Wataru Kakegawa
A1 Amber J. Clayton
A1 Veronica T. Chang
A1 Maura Ferrer-Ferrer
A1 Eriko Miura
A1 Rahul Kaushik
A1 Masashi Ikeno
A1 Yuki Morioka
A1 Yuka Takeuchi
A1 Tatsuya Shimada
A1 Shintaro Otsuka
A1 Stoyan Stoyanov
A1 Masahiko Watanabe
A1 Kosei Takeuchi
A1 Alexander Dityatev
A1 A. Radu Aricescu
A1 Michisuke Yuzaki
YR 2020
UL http://biorxiv.org/content/early/2020/02/27/2020.02.27.967836.abstract
AB Neuronal synapses undergo structural and functional changes throughout life, 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 report the design and characterization of CPTX, a synthetic synaptic organizer combining structural elements from cerebellin-1 and neuronal pentraxin-1 to interact with presynaptic neurexins and postsynaptic AMPA-type ionotropic glutamate receptors. CPTX induced the formation of excitatory synapses in vitro and in vivo and 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 novel structure-guided biologics that can efficiently repair or remodel neuronal circuits.One Sentence Summary Structural biology information was used to design CPTX, a synthetic protein that induces functional excitatory synapses and restores normal behaviors in mouse models of neurological diseases.