Tyro3 promotes the maturation of glutamatergic synapses

Sheng Miao, Lawrence Fourgeaud, Patrick G. Burrola, Shani Stern, Yuhan Zhang, Kaisa E. Happonen, Sammy Weiser Novak, Fred H. Gage, Greg Lemke

Research output: Contribution to journalArticlepeer-review


The receptor tyrosine kinase Tyro3 is abundantly expressed in neurons of the neocortex, hippocampus, and striatum, but its role in these cells is unknown. We found that neuronal expression of this receptor was markedly up-regulated in the postnatal mouse neocortex immediately prior to the final development of glutamatergic synapses. In the absence of Tyro3, cortical and hippocampal synapses never completed end-stage differentiation and remained electrophysiologically and ultrastructurally immature. Tyro3−/− cortical neurons also exhibited diminished plasma membrane expression of the GluA2 subunits of AMPA-type glutamate receptors, which are essential to mature synaptic function. Correspondingly, GluA2 membrane insertion in wild-type neurons was stimulated by Gas6, a Tyro3 ligand widely expressed in the postnatal brain. Behaviorally, Tyro3−/− mice displayed learning enhancements in spatial recognition and fear-conditioning assays. Together, these results demonstrate that Tyro3 promotes the functional maturation of glutamatergic synapses by driving plasma membrane translocation of GluA2 AMPA receptor subunits.

Original languageEnglish
Article number1327423
JournalFrontiers in Neuroscience
StatePublished - 2024

Bibliographical note

Publisher Copyright:
Copyright © 2024 Miao, Fourgeaud, Burrola, Stern, Zhang, Happonen, Novak, Gage and Lemke.


  • GluA2
  • Hebbian learning
  • phosphatidylserine
  • receptor tyrosine kinase
  • synaptic maturation

ASJC Scopus subject areas

  • General Neuroscience


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