Neuropilin-2/PlexinA3 Receptors Associate with GluA1 and Mediate Sema3F-Dependent Homeostatic Scaling in Cortical Neurons

Neuron. 2017 Dec 6;96(5):1084-1098.e7. doi: 10.1016/j.neuron.2017.10.029. Epub 2017 Nov 16.

Abstract

Regulation of AMPA-type glutamate receptor (AMPAR) number at synapses is a major mechanism for controlling synaptic strength during homeostatic scaling in response to global changes in neural activity. We show that the secreted guidance cue semaphorin 3F (Sema3F) and its neuropilin-2 (Npn-2)/plexinA3 (PlexA3) holoreceptor mediate homeostatic plasticity in cortical neurons. Sema3F-Npn-2/PlexA3 signaling is essential for cell surface AMPAR homeostatic downscaling in response to an increase in neuronal activity, Npn-2 associates with AMPARs, and Sema3F regulates this interaction. Therefore, Sema3F-Npn-2/PlexA3 signaling controls both synapse development and synaptic plasticity.

Keywords: AMPA receptor; Neuropilin-2; Plexin receptor; Sema3F; homeostatic plasticity; semaphorin.

MeSH terms

  • Animals
  • Bicuculline / pharmacology
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiology*
  • Female
  • GABA Antagonists / pharmacology
  • Homeostasis / drug effects
  • Male
  • Membrane Proteins / drug effects
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / drug effects
  • Nerve Tissue Proteins / physiology*
  • Neuronal Plasticity / physiology
  • Neurons / drug effects
  • Neurons / physiology*
  • Neuropilin-2 / drug effects
  • Neuropilin-2 / physiology*
  • Primary Cell Culture
  • Rats, Sprague-Dawley
  • Receptors, AMPA / drug effects
  • Receptors, AMPA / physiology*
  • Synapses / physiology

Substances

  • GABA Antagonists
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Neuropilin-2
  • Receptors, AMPA
  • Sema3f protein, mouse
  • glutamate receptor ionotropic, AMPA 1
  • Bicuculline