2. Academic Validation
  3. Positioning of AMPA Receptor-Containing Endosomes Regulates Synapse Architecture

Positioning of AMPA Receptor-Containing Endosomes Regulates Synapse Architecture

  • Cell Rep. 2015 Nov 3;13(5):933-43. doi: 10.1016/j.celrep.2015.09.062.
Marta Esteves da Silva 1,  Max Adrian 1,  Philipp Schätzle 1,  Joanna Lipka 2,  Takuya Watanabe 3,  Sukhee Cho 3,  Kensuke Futai 3,  Corette J Wierenga 1,  Lukas C Kapitein 4,  Casper C Hoogenraad 5
Affiliations

Affiliations

  • 1 Cell Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
  • 2 Cell Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands; International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland.
  • 3 Department of Psychiatry, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
  • 4 Cell Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands; Department of Neuroscience, Erasmus Medical Center, 3015 GE Rotterdam, the Netherlands. Electronic address: l.kapitein@uu.nl.
  • 5 Cell Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands; Department of Neuroscience, Erasmus Medical Center, 3015 GE Rotterdam, the Netherlands. Electronic address: c.hoogenraad@uu.nl.
PMID: 26565907 DOI: 10.1016/j.celrep.2015.09.062
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.

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