Glutamate receptor targeting in the postsynaptic spine involves mechanisms that are independent of myosin Va

Eur J Neurosci. 2001 May;13(9):1722-32. doi: 10.1046/j.0953-816x.2001.01553.x.


Targeting of glutamate receptors (GluRs) to synapses involves rapid movement of intracellular receptors. This occurs in forms of synaptic upregulation of receptors, such as long-term potentiation. Thus, many GluRs are retained in a cytoplasmic pool in dendrites, and are transported to synapses for upregulation, presumably via motor proteins such as myosins travelling along cytoskeletal elements that extend up into the spine. In this ultrastructural immunogold study of the cerebellar cortex, we compared synapses between normal rats/mice and dilute lethal mutant mice. These mutant mice lack myosin Va, which has been implicated in protein trafficking at synapses. The postsynaptic spine in the cerebellum lacks the inositol trisphosphate receptor (IP3R) -laden reticular tubules that are found in normal mice and rats (Takagishi et al., Neurosci. Lett., 1996, 215, 169). Thus, we tested the hypothesis that myosin Va is necessary for transport of GluRs and associated proteins to spine synapses. We found that these spines retain a normal distribution of (i) GluRs (delta 1/2, GluR2/3 and mGluR1alpha), (ii) at least one associated MAGUK (membrane-associated guanylate kinase) protein, (iii) Homer (which interacts with mGluR1alpha and IP3Rs), (iv) the actin cytoskeleton, (v) the reticulum-associated protein BiP, and (vi) the motor-associated protein, dynein light chain. Thus, while myosin Va may maintain the IP3R-laden reticulum in the spine for proper calcium regulation, other mechanisms must be involved in the delivery of GluRs and associated proteins to synapses. Other possible mechanisms include diffusion along the extrasynaptic membrane and delivery via other motors running along the spine's actin cytoskeleton.

MeSH terms

  • Actins / metabolism
  • Animals
  • Calcium Channels / metabolism
  • Carrier Proteins / metabolism
  • Cerebellar Cortex / metabolism*
  • Cerebellar Cortex / ultrastructure
  • Dendrites / metabolism*
  • Dendrites / ultrastructure
  • Drosophila Proteins*
  • Dyneins
  • Guanylate Kinases
  • Heat-Shock Proteins*
  • Homer Scaffolding Proteins
  • Immunohistochemistry
  • Inositol 1,4,5-Trisphosphate Receptors
  • Mice
  • Mice, Mutant Strains
  • Microscopy, Electron
  • Molecular Chaperones / metabolism
  • Myosins / metabolism*
  • Neuropeptides / metabolism
  • Nucleoside-Phosphate Kinase / metabolism
  • Protein Transport / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, Glutamate / metabolism*
  • Synaptic Membranes / metabolism*
  • Synaptic Membranes / ultrastructure


  • Actins
  • Calcium Channels
  • Carrier Proteins
  • Drosophila Proteins
  • Heat-Shock Proteins
  • Homer Scaffolding Proteins
  • Inositol 1,4,5-Trisphosphate Receptors
  • Molecular Chaperones
  • Neuropeptides
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Glutamate
  • homer protein, Drosophila
  • Nucleoside-Phosphate Kinase
  • Guanylate Kinases
  • Myosins
  • Dyneins
  • molecular chaperone GRP78