Postsynaptic positioning of endocytic zones and AMPA receptor cycling by physical coupling of dynamin-3 to Homer.
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2007-09
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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.
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Lu, Jiuyi, Thomas D Helton, Thomas A Blanpied, Bence Rácz, Thomas M Newpher, Richard J Weinberg and Michael D Ehlers (2007). Postsynaptic positioning of endocytic zones and AMPA receptor cycling by physical coupling of dynamin-3 to Homer. Neuron, 55(6). pp. 874–889. 10.1016/j.neuron.2007.06.041 Retrieved from https://hdl.handle.net/10161/27389.
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Thomas Mark Newpher
I teach, mentor, and advise for Duke's Undergraduate Studies in Neuroscience program, and serve as the Associate Director of Undergraduate Studies in Neuroscience. I also direct the Summer Neuroscience Program of Research in the Duke Institute for Brain Sciences. I earned my Ph.D. in molecular biology from Case Western Reserve University. After graduate school, I came to Duke University to receive postdoctoral training in the Neurobiology Department, where my research focused on identifying molecular mechanisms that underlie learning-related synaptic plasticity.
As the director of the Summer Neuroscience Program, I provide mentorship and professional development opportunities for undergraduate research fellows. My courses use a variety of team-based learning activities to promote critical thinking skills, foster collaboration among students, and create an engaging, student-centered classroom experience. As a co-PI in the Duke Team-Based Learning lab, I study the impacts of collaborative learning on student performance and classroom dynamics.
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