Department of Psychiatry, Brudnick Neuropsychiatric Research Institute; Graduate School of Biomedical Sciences, Neuroscience Program
Cell Biology | Molecular and Cellular Neuroscience
Lateral diffusion in the membrane and endosomal trafficking both contribute to the addition and removal of AMPA receptors (AMPARs) at postsynaptic sites. However, the spatial coordination between these mechanisms has remained unclear, because little is known about the dynamics of AMPAR-containing endosomes. In addition, how the positioning of AMPAR-containing endosomes affects synapse organization and functioning has never been directly explored. Here, we used live-cell imaging in hippocampal neuron cultures to show that intracellular AMPARs are transported in Rab11-positive recycling endosomes, which frequently enter dendritic spines and depend on the microtubule and actin cytoskeleton. By using chemically induced dimerization systems to recruit kinesin (KIF1C) or myosin (MyosinV/VI) motors to Rab11-positive recycling endosomes, we controlled their trafficking and found that induced removal of recycling endosomes from spines decreases surface AMPAR expression and PSD-95 clusters at synapses. Our data suggest a mechanistic link between endosome positioning and postsynaptic structure and composition.
AMPA receptors, KIF1C, actin, cytoskeleton, dendritic spine, intracellular transport, kinesin, microtubule, myosin, myosinV, myosinVI, synaptic plasticity
DOI of Published Version
Cell Rep. 2015 Nov 3;13(5):933-43. doi: 10.1016/j.celrep.2015.09.062. Epub 2015 Oct 22. Link to article on publisher's site
Esteves da Silva, Marta; Adrian, Max; Schatzle, Philipp; Lipka, Joanna; Watanabe, Takuya; Cho, Sukhee; Futai, Kensuke; Wierenga, Corette J.; Kapitein, Lukas C.; and Hoogenraad, Casper C., "Positioning of AMPA Receptor-Containing Endosomes Regulates Synapse Architecture" (2015). Open Access Articles. 2672.
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