Bernard C, Exposito-Alonso D, Selten M, Sanalidou S, Hanusz-Godoy A, Aguilera A, Hamid F, Oozeer F, Maeso P, Allison L, Russell M, Fleck RA, Rico B, Marín O (2022) Cortical wiring by synapse type-specific control of local protein synthesis. Science 378: eabm7466

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.

Pubmed: 36423280