Positioning of AMPA Receptor-Containing Endosomes Regulates Synapse Architecture

• Main Authors: Marta Esteves da Silva, Max Adrian, Philipp Schätzle, Joanna Lipka, Takuya Watanabe, Sukhee Cho, Kensuke Futai, Corette J. Wierenga, Lukas C. Kapitein, Casper C. Hoogenraad
• Format: Article
• Language: English
• Published: Elsevier 2015-11-01
• Series: Cell Reports
• Subjects: synaptic plasticity; intracellular transport; AMPA receptors; dendritic spine; cytoskeleton; microtubule; actin; myosin; kinesin; KIF1C; myosinV; myosinVI
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124715011043

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.