UMMS Affiliation
Department of Psychiatry, Brudnick Neuropsychiatric Research Institute; Graduate School of Biomedical Sciences, Neuroscience Program
Publication Date
11-3-2015
Document Type
Article
Disciplines
Cell Biology | Molecular and Cellular Neuroscience
Abstract
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.
Keywords
AMPA receptors, KIF1C, actin, cytoskeleton, dendritic spine, intracellular transport, kinesin, microtubule, myosin, myosinV, myosinVI, synaptic plasticity
DOI of Published Version
10.1016/j.celrep.2015.09.062
Source
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
Journal/Book/Conference Title
Cell reports
Related Resources
PubMed ID
26565907
Repository Citation
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.
https://escholarship.umassmed.edu/oapubs/2672
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Comments
Co-author Sukhee Cho is a doctoral student in the Neuroscience Program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.