Postsynaptic positioning of endocytic zones and AMPA receptor cycling by physical coupling of dynamin-3 to Homer.
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.
Lu
Jiuyi
J
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
Helton
Thomas D
TD
Blanpied
Thomas A
TA
Rácz
Bence
B
Newpher
Thomas M
TM
Weinberg
Richard J
RJ
Ehlers
Michael D
MD
D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D002966:Clathrin / Q000502:physiology; D004247:DNA / Q000235:genetics; D034286:Dynamin III / Q000737:chemistry / Q000502:physiology*; D004594:Electrophysiology; D020558:GTP Phosphohydrolases / Q000172:deficiency / Q000235:genetics; D000072233:Homer Scaffolding Proteins; D006801:Humans; D007150:Immunohistochemistry; D050356:Lipid Metabolism / Q000502:physiology; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D034622:RNA Interference / Q000502:physiology; D018091:Receptors, AMPA / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D022161:Transport Vesicles / Q000502:physiology* / Q000648:ultrastructure
D002352:Carrier Proteins; D002966:Clathrin; D000072233:Homer Scaffolding Proteins; D018091:Receptors, AMPA; D004247:DNA; D020558:GTP Phosphohydrolases; D034286:Dynamin III