title: Postsynaptic positioning of endocytic zones and AMPA receptor cycling by physical coupling of dynamin-3 to Homer.
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.
authors: Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
authors: Jiuyi
authors: J
authors: Lu
authors: Thomas D
authors: TD
authors: Helton
authors: Thomas A
authors: TA
authors: Blanpied
authors: Bence
authors: B
authors: Rácz
authors: Thomas M
authors: TM
authors: Newpher
authors: Richard J
authors: RJ
authors: Weinberg
authors: Michael D
authors: MD
authors: Ehlers
mesh_terms: 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
chemical_list: D002352:Carrier Proteins; D002966:Clathrin; D000072233:Homer Scaffolding Proteins; D018091:Receptors, AMPA; D004247:DNA; D020558:GTP Phosphohydrolases; D034286:Dynamin III