Postsynaptic Positioning of Endocytic Zones and AMPA Receptor Cycling by Physical Coupling of Dynamin-3 to Homer

Jiuyi Lu, Thomas D. Helton, Thomas A. Blanpied, B. Rácz, Thomas M. Newpher, Richard J. Weinberg, Michael D. Ehlers

Research output: Contribution to journalArticle

172 Citations (Scopus)

Abstract

Endocytosis of AMPA receptors and other postsynaptic cargo occurs at endocytic zones (EZs), stably positioned sites of clathrin adjacent to the postsynaptic density (PSD). The tight localization of postsynaptic endocytosis is thought to control spine composition and regulate synaptic transmission. However, the mechanisms that situate the EZ near the PSD and the role of spine endocytosis in synaptic transmission are unknown. Here, we report that a physical link between dynamin-3 and the postsynaptic adaptor Homer positions the EZ near the PSD. Disruption of dynamin-3 or its interaction with Homer uncouples the PSD from the EZ, resulting in synapses lacking postsynaptic clathrin. Loss of the EZ leads to a loss of synaptic AMPA receptors and reduced excitatory synaptic transmission that corresponds with impaired synaptic recycling. Thus, a physical link between the PSD and the EZ ensures localized endocytosis and recycling by recapturing and maintaining a proximate pool of cycling AMPA receptors.

Original languageEnglish
Pages (from-to)874-889
Number of pages16
JournalNeuron
Volume55
Issue number6
DOIs
Publication statusPublished - Sep 20 2007

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Dynamin III
Post-Synaptic Density
AMPA Receptors
Endocytosis
Synaptic Transmission
Clathrin
Recycling
Spine
Neurotransmitter Receptor
Synapses

Keywords

  • CELLBIO
  • MOLNEURO
  • SIGNALING

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Lu, J., Helton, T. D., Blanpied, T. A., Rácz, B., Newpher, T. M., Weinberg, R. J., & Ehlers, M. D. (2007). Postsynaptic Positioning of Endocytic Zones and AMPA Receptor Cycling by Physical Coupling of Dynamin-3 to Homer. Neuron, 55(6), 874-889. https://doi.org/10.1016/j.neuron.2007.06.041

Postsynaptic Positioning of Endocytic Zones and AMPA Receptor Cycling by Physical Coupling of Dynamin-3 to Homer. / Lu, Jiuyi; Helton, Thomas D.; Blanpied, Thomas A.; Rácz, B.; Newpher, Thomas M.; Weinberg, Richard J.; Ehlers, Michael D.

In: Neuron, Vol. 55, No. 6, 20.09.2007, p. 874-889.

Research output: Contribution to journalArticle

Lu, Jiuyi ; Helton, Thomas D. ; Blanpied, Thomas A. ; Rácz, B. ; Newpher, Thomas M. ; Weinberg, Richard J. ; Ehlers, Michael D. / Postsynaptic Positioning of Endocytic Zones and AMPA Receptor Cycling by Physical Coupling of Dynamin-3 to Homer. In: Neuron. 2007 ; Vol. 55, No. 6. pp. 874-889.
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