Defects in synaptic plasticity, reduced nmda-receptor transport, and instability of postsynaptic density proteins in mice lacking microtubule-associated protein 1a

Yosuke Takei, Yayoi S. Kikkawa, Nafiseh Atapour, Takao K. Hensch, Nobutaka Hirokawa

Research output: Contribution to journalArticleResearchpeer-review

20 Citations (Scopus)

Abstract

Microtubule-associated protein 1A (MAP1A) is a member of the major non-motor microtubule-binding proteins. It has been suggested that MAP1A tethers NMDA receptors (NRs) to the cytoskeleton by binding with proteins postsynaptic density (PSD)-93 and PSD-95, although the function of MAP1A in vivo remains elusive. The present study demonstrates that mouse MAP1A plays an essential role in maintaining synaptic plasticity through an analysis ofMAP1Aknock-out mice. The mice exhibited learning disabilities, which correlated with decreased long-term potentiation and long-term depression in the hippocampal neurons, as well as a concomitant reduction in the extent of NR-dependent EPSCs. Surface expression of NR2A and NR2B subunits also decreased. Enhanced activity-dependent degradation of PSD-93 and reduced transport of NR2A/2B in dendrites was likely responsible for altered receptor function in neurons lacking MAP1A. These data suggest that tethering of NR2A/2B with the cytoskeleton through MAP1A is fundamental for synaptic function.

Original languageEnglish
Pages (from-to)15539-15554
Number of pages16
JournalJournal of Neuroscience
Volume35
Issue number47
DOIs
Publication statusPublished - 25 Nov 2015
Externally publishedYes

Keywords

  • Learning and memory
  • Microtubule-associated protein
  • Neuronal plasticity
  • NMDA receptor
  • Transport

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