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

Clémence Bernard; David Exposito-Alonso; Martijn Selten; Stella Sanalidou; Alicia Hanusz-Godoy; Alfonso Aguilera; Fursham Hamid; Fazal Oozeer; Patricia Maeso; Leanne Allison; Matthew Russell; Roland A. Fleck; Beatriz Rico; Oscar Marín

doi:10.1126/science.abm7466

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

Clémence Bernard, David Exposito-Alonso, Martijn Selten, Stella Sanalidou, Alicia Hanusz-Godoy, Alfonso Aguilera, Fursham Hamid, Fazal Oozeer, Patricia Maeso, Leanne Allison, Matthew Russell, Roland A. Fleck, Beatriz Rico^*, Oscar Marín

^*Corresponding author for this work

King's College London

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

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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.

Original language	English
Journal	Science
Volume	378
Issue number	6622
DOIs	https://doi.org/10.1126/science.abm7466
Publication status	Published - 25 Nov 2022

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title = "Cortical wiring by synapse type–specific control of local protein synthesis",

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.",

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T1 - Cortical wiring by synapse type–specific control of local protein synthesis

AU - Bernard, Clémence

AU - Exposito-Alonso, David

AU - Selten, Martijn

AU - Sanalidou, Stella

AU - Hanusz-Godoy, Alicia

AU - Aguilera, Alfonso

AU - Hamid, Fursham

AU - Oozeer, Fazal

AU - Maeso, Patricia

AU - Allison, Leanne

AU - Russell, Matthew

AU - Fleck, Roland A.

AU - Rico, Beatriz

AU - Marín, Oscar

PY - 2022/11/25

Y1 - 2022/11/25

N2 - 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.

AB - 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.

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VL - 378

JO - Science

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

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