Cortical wiring by synapse type-specific control of local protein synthesis

• Published in: Science (American Association for the Advancement of Science) Vol. 378; no. 6622; p. eabm7466
• Main Authors: Bernard, Clémence, Exposito-Alonso, David, Selten, Martijn, Sanalidou, Stella, Hanusz-Godoy, Alicia, Aguilera, Alfonso, Hamid, Fursham, Oozeer, Fazal, Maeso, Patricia, Allison, Leanne, Russell, Matthew, Fleck, Roland A, Rico, Beatriz, Marín, Oscar
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 25.11.2022
• Subjects: Anatomy; Animals; Autism; Autism Spectrum Disorders; Axon guidance; Axons; Brain; CACNG2 protein; Calcium channels (voltage-gated); Cell adhesion; Cell adhesion molecules; Cell size; Cerebral cortex; Cerebral Cortex - metabolism; Coding; Decentralized control; ErbB-2 protein; Gene sequencing; Genetics; Glutamatergic transmission; Growth factors; In vivo methods and tests; Interneurons; Interneurons - metabolism; Kinases; Mice; Mutation; Neocortex; Nervous system; Neurodevelopmental disorders; Neurons; Parvalbumin; Photovoltaic cells; Protein Biosynthesis; Protein synthesis; Protein-tyrosine kinase receptors; Proteins; Rapamycin; Receptor, ErbB-4 - genetics; Receptor, ErbB-4 - metabolism; Receptors; Ribonucleic acid; RNA; RNA, Messenger - genetics; RNA, Messenger - metabolism; Seizures; Signal transduction; Signaling; Synapses; Synapses - metabolism; Synaptogenesis; Translation; Tuberous Sclerosis Complex 2 Protein - genetics; Tuberous Sclerosis Complex 2 Protein - metabolism; Tyrosine; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors; γ-Aminobutyric acid
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.abm7466

Neurons use local protein synthesis to support their morphological complexity, which requires independent control across multiple subcellular compartments up to the level of individual synapses. We identify a signaling pathway that regulates the local synthesis of proteins required to form excitatory synapses on parvalbumin-expressing (PV ) interneurons in the mouse cerebral cortex. This process involves regulation of the TSC subunit 2 (Tsc2) by the Erb-B2 receptor tyrosine kinase 4 (ErbB4), which enables local control of messenger RNA {mRNA} translation in a cell type-specific and synapse type-specific manner. Ribosome-associated mRNA profiling reveals a molecular program of synaptic proteins downstream of ErbB4 signaling required to form excitatory inputs on PV interneurons. Thus, specific connections use local protein synthesis to control synapse formation in the nervous system.