Mind bomb-2 is an E3 ligase that ubiquitinates the N-methyl-D-aspartate receptor NR2B subunit in a phosphorylation-dependent manner. Academic Article uri icon

abstract

  • The N-methyl-D-aspartate receptor (NMDAR) plays a critical role in synaptic plasticity. Post-translational modifications of NMDARs, such as phosphorylation, alter both the activity and trafficking properties of NMDARs. Ubiquitination is increasingly being recognized as another post-translational modification that can alter synaptic protein composition and function. We identified Mind bomb-2 as an E3 ubiquitin ligase that interacts with and ubiquitinates the NR2B subunit of the NMDAR in mammalian cells. The protein-protein interaction and the ubiquitination of the NR2B subunit were found to be enhanced in a Fyn phosphorylation-dependent manner. Immunocytochemical studies reveal that Mind bomb-2 is localized to postsynaptic sites and colocalizes with the NMDAR in apical dendrites of hippocampal neurons. Furthermore, we show that NMDAR activity is down-regulated by Mind bomb-2. These results identify a specific E3 ubiquitin ligase as a novel interactant with the NR2B subunit and suggest a possible mechanism for the regulation of NMDAR function involving both phosphorylation and ubiquitination.

published proceedings

  • J Biol Chem

altmetric score

  • 1

author list (cited authors)

  • Jurd, R., Thornton, C., Wang, J., Luong, K., Phamluong, K., Kharazia, V., Gibb, S. L., & Ron, D

citation count

  • 62

complete list of authors

  • Jurd, Rachel||Thornton, Claire||Wang, Jun||Luong, Ken||Phamluong, Khanhky||Kharazia, Viktor||Gibb, Stuart L||Ron, Dorit

publication date

  • October 2007