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

Ronald S. Petralia, Ya Xian Wang, Nathalie Sans, Paul F Worley, John A. Hammer, Robert J. Wenthold

Research output: Contribution to journalArticle

Abstract

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 mGluR1α), (ii) at least one associated MAGUK (membrane-associated guanylate kinase) protein, (iii) Homer (which interacts with mGluR1α 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.

Original languageEnglish (US)
Pages (from-to)1722-1732
Number of pages11
JournalEuropean Journal of Neuroscience
Volume13
Issue number9
DOIs
StatePublished - 2001

Fingerprint

Glutamate Receptors
Myosins
Synapses
Spine
Reticulum
Proteins
Actin Cytoskeleton
Up-Regulation
Guanylate Kinases
Dyneins
Cerebellar Cortex
Neurotransmitter Receptor
Long-Term Potentiation
Normal Distribution
Protein Transport
Inositol
Dendrites
Running
Cerebellum
Calcium

Keywords

  • AMPA
  • Cerebellum
  • Delta
  • dilute mouse
  • Rat

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Glutamate receptor targeting in the postsynaptic spine involves mechanisms that are independent of myosin Va. / Petralia, Ronald S.; Wang, Ya Xian; Sans, Nathalie; Worley, Paul F; Hammer, John A.; Wenthold, Robert J.

In: European Journal of Neuroscience, Vol. 13, No. 9, 2001, p. 1722-1732.

Research output: Contribution to journalArticle

Petralia, Ronald S. ; Wang, Ya Xian ; Sans, Nathalie ; Worley, Paul F ; Hammer, John A. ; Wenthold, Robert J. / Glutamate receptor targeting in the postsynaptic spine involves mechanisms that are independent of myosin Va. In: European Journal of Neuroscience. 2001 ; Vol. 13, No. 9. pp. 1722-1732.
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