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

Science. 2022 Nov 25;378(6622):eabm7466. doi: 10.1126/science.abm7466. Epub 2022 Nov 25.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebral Cortex* / metabolism
  • Interneurons* / metabolism
  • Mice
  • Protein Biosynthesis*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, ErbB-4* / genetics
  • Receptor, ErbB-4* / metabolism
  • Synapses* / metabolism
  • Tuberous Sclerosis Complex 2 Protein* / genetics
  • Tuberous Sclerosis Complex 2 Protein* / metabolism

Substances

  • Receptor, ErbB-4
  • RNA, Messenger
  • Tsc2 protein, mouse
  • Tuberous Sclerosis Complex 2 Protein