Postsynaptic density protein 95 (PSD-95) is transported by KIF5 to dendritic regions

Mol Brain. 2019 Nov 21;12(1):97. doi: 10.1186/s13041-019-0520-x.

Abstract

Postsynaptic density protein 95 (PSD-95) is a pivotal postsynaptic scaffolding protein in excitatory neurons. Although the transport and regulation of PSD-95 in synaptic regions is well understood, dendritic transport of PSD-95 before synaptic localization still remains to be clarified. To evaluate the role of KIF5, conventional kinesin, in the dendritic transport of PSD-95 protein, we expressed a transport defective form of KIF5A (ΔMD) that does not contain the N-terminal motor domain. Expression of ΔMD significantly decreased PSD-95 level in the dendrites. Consistently, KIF5 was associated with PSD-95 in in vitro and in vivo assays. This interaction was mediated by the C-terminal tail regions of KIF5A and the third PDZ domain of PSD-95. Additionally, the ADPDZ3 (the association domain of NMDA receptor and PDZ3 domain) expression significantly reduced the levels of PSD-95, glutamate receptor 1 (GluA1) in dendrites. The association between PSD-95 and KIF5A was dose-dependent on Staufen protein, suggesting that the Staufen plays a role as a regulatory role in the association. Taken together, our data suggest a new mechanism for dendritic transport of the AMPA receptor-PSD-95.

Keywords: Dendritic transport; Glutamate receptor 1; KIF5; PSD-95.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dendrites / metabolism*
  • Disks Large Homolog 4 Protein / chemistry
  • Disks Large Homolog 4 Protein / metabolism*
  • HEK293 Cells
  • Humans
  • Kinesin / chemistry
  • Kinesin / metabolism*
  • Mice
  • Models, Biological
  • Mutant Proteins / metabolism
  • PDZ Domains
  • Protein Binding
  • Protein Transport
  • RNA-Binding Proteins / metabolism
  • Rats, Sprague-Dawley
  • Receptors, AMPA / metabolism

Substances

  • Disks Large Homolog 4 Protein
  • Kif5A protein, mouse
  • Mutant Proteins
  • RNA-Binding Proteins
  • Receptors, AMPA
  • Stau1 protein, rat
  • Kinesin
  • glutamate receptor ionotropic, AMPA 1