Loss of F-box only protein 2 (Fbxo2) disrupts levels and localization of select NMDA receptor subunits, and promotes aberrant synaptic connectivity

Graham Atkin, Shannon Moore, Yuan Lu, Rick F. Nelson, Nathan Tipper, Gautam Rajpal, Jack Hunt, William Tennant, Johannes W Hell, Geoffrey G. Murphy, Henry Paulson

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

NMDA receptors (NMDARs) play an essential role in some forms of synaptic plasticity, learning, and memory. Therefore, these receptors are highly regulated with respect to their localization, activation, and abundance both within and on the surface of mammalian neurons. Fundamental questions remain, however, regarding how this complex regulation is achieved. Using cell-based models and F-box Only Protein 2 (Fbxo2) knock-out mice, we found that the ubiquitin ligase substrate adaptor protein Fbxo2, previously reported to facilitate the degradation of the NMDAR subunit GluN1 in vitro, also functions to regulate GluN1 and GluN2A subunit levels in the adult mouse brain. In contrast, GluN2B subunit levels are not affected by the loss of Fbxo2. The loss of Fbxo2 results in greater surface localization of GluN1 and GluN2A, together with increases in the synaptic markers PSD-95 and Vglut1. These synaptic changes do not manifest as neurophysiological differences or alterations in dendritic spine density in Fbxo2 knock-out mice, but result instead in increased axo-dendritic shaft synapses. Together, these findings suggest that Fbxo2 controls the abundance and localization of specific NMDAR subunits in the brain and may influence synapse formation and maintenance.

Original languageEnglish (US)
Pages (from-to)6165-6178
Number of pages14
JournalJournal of Neuroscience
Volume35
Issue number15
DOIs
StatePublished - Apr 15 2015

Fingerprint

F-Box Proteins
N-Methyl-D-Aspartate Receptors
Knockout Mice
Synapses
Dendritic Spines
Neuronal Plasticity
Brain
Ligases
Ubiquitin
Maintenance
Learning
Neurons

Keywords

  • Fbxo2
  • GluN1
  • GluN2A
  • NMDA
  • Synapse

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Loss of F-box only protein 2 (Fbxo2) disrupts levels and localization of select NMDA receptor subunits, and promotes aberrant synaptic connectivity. / Atkin, Graham; Moore, Shannon; Lu, Yuan; Nelson, Rick F.; Tipper, Nathan; Rajpal, Gautam; Hunt, Jack; Tennant, William; Hell, Johannes W; Murphy, Geoffrey G.; Paulson, Henry.

In: Journal of Neuroscience, Vol. 35, No. 15, 15.04.2015, p. 6165-6178.

Research output: Contribution to journalArticle

Atkin, Graham ; Moore, Shannon ; Lu, Yuan ; Nelson, Rick F. ; Tipper, Nathan ; Rajpal, Gautam ; Hunt, Jack ; Tennant, William ; Hell, Johannes W ; Murphy, Geoffrey G. ; Paulson, Henry. / Loss of F-box only protein 2 (Fbxo2) disrupts levels and localization of select NMDA receptor subunits, and promotes aberrant synaptic connectivity. In: Journal of Neuroscience. 2015 ; Vol. 35, No. 15. pp. 6165-6178.
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