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SAP97 and CASK mediate sorting of NMDA receptors through a previously unknown secretory pathway.

Nature neuroscience | Aug 28, 2009

Synaptic plasticity is dependent on the differential sorting, delivery and retention of neurotransmitter receptors, but the mechanisms underlying these processes are poorly understood. We found that differential sorting of glutamate receptor subtypes began in the endoplasmic reticulum of rat hippocampal neurons. As AMPA receptors (AMPARs) were trafficked to the plasma membrane via the conventional somatic Golgi network, NMDA receptors (NMDARs) were diverted from the somatic endoplasmic reticulum into a specialized endoplasmic reticulum subcompartment that bypasses somatic Golgi, merging instead with dendritic Golgi outposts. This endoplasmic reticulum subcompartment was composed of highly mobile vesicles containing the NMDAR subunits NR1 and NR2B, the microtubule-dependent motor protein KIF17, and the postsynaptic adaptor proteins CASK and SAP97. Our data demonstrate that the retention and trafficking of NMDARs in this endoplasmic reticulum subcompartment requires both CASK and SAP97. These findings indicate that NMDARs are sorted away from AMPARs via a non-conventional secretory pathway that utilizes dendritic Golgi outposts.

Pubmed ID: 19620977 RIS Download

Mesh terms: Adaptor Proteins, Signal Transducing | Animals | Bodily Secretions | Cell Compartmentation | Cell Line | Cells, Cultured | Dendrites | Endoplasmic Reticulum | Golgi Apparatus | Guanylate Kinases | Hippocampus | Humans | Kinesin | Membrane Proteins | Neurons | Protein Transport | Rats | Rats, Sprague-Dawley | Receptors, AMPA | Receptors, N-Methyl-D-Aspartate | Signal Transduction

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Associated grants

  • Agency: NIDA NIH HHS, Id: P01 DA019695-01A2
  • Agency: NINDS NIH HHS, Id: R56 NS043782-06
  • Agency: NIDA NIH HHS, Id: DA016758
  • Agency: NINDS NIH HHS, Id: R56 NS043782
  • Agency: NIDA NIH HHS, Id: DA019695
  • Agency: NINDS NIH HHS, Id: NS043782
  • Agency: NIDA NIH HHS, Id: P01 DA019695
  • Agency: NINDS NIH HHS, Id: R01 NS041091
  • Agency: NEI NIH HHS, Id: P30 EY013079
  • Agency: NIDA NIH HHS, Id: DA13602
  • Agency: NIDA NIH HHS, Id: R01 DA016758
  • Agency: NINDS NIH HHS, Id: R01 NS043782
  • Agency: NEI NIH HHS, Id: R01 EY013145
  • Agency: NIDA NIH HHS, Id: R01 DA013602
  • Agency: NEI NIH HHS, Id: R01 EY013145-04
  • Agency: NEI NIH HHS, Id: P30 EY013079-109003
  • Agency: NINDS NIH HHS, Id: R01 NS041091-04
  • Agency: NINDS NIH HHS, Id: R01 NS043782-05

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