biostudies-literatureBernard CMedical Research CouncilWellcome Trusteabm7466https://www.ebi.ac.uk/biostudies/studies/S-EPMC7618116biostudies-literatureUnknown378(6622)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⁺ intScience (New York, N.Y.)Cortical wiring by synapse type-specific control of local protein synthesis.PMC7618116MR/W006251/1MR/N026063/1202758MR/S010785/1Oozeer FHamid FAllison LSelten MRico BSanalidou SHanusz-Godoy ARussell MMarin OExposito-Alonso DBernard CAguilera AMaeso PFleck RAfalseCortical wiring by synapse type-specific control of local protein synthesis.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⁺ int2022-01-01T00:00:00Z2022 Nov2026-06-01T06:32:12.707Z2026-04-08T09:56:26.786ZS-EPMC76181163642328010.1126/science.abm7466