title: Positioning of AMPA Receptor-Containing Endosomes Regulates Synapse Architecture.
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.
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
authors.forename: Marta
authors.initials: M
authors.lastname: Esteves da Silva
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
authors.forename: Max
authors.initials: M
authors.lastname: Adrian
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
authors.forename: Philipp
authors.initials: P
authors.lastname: Schätzle
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands; International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Lipka
authors.affiliation: Department of Psychiatry, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Takuya
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Psychiatry, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Sukhee
authors.initials: S
authors.lastname: Cho
authors.affiliation: Department of Psychiatry, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Futai
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
authors.forename: Corette J
authors.initials: CJ
authors.lastname: Wierenga
authors.affiliation: 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.
authors.forename: Lukas C
authors.initials: LC
authors.lastname: Kapitein
authors.affiliation: 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.
authors.forename: Casper C
authors.initials: CC
authors.lastname: Hoogenraad
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000378:metabolism / Q000648:ultrastructure; D011992:Endosomes / Q000378:metabolism*; D005260:Female; D016547:Kinesins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009218:Myosins / Q000378:metabolism; D051381:Rats; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
chemical_list: D016547:Kinesins; D009218:Myosins; D018091:Receptors, AMPA; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins
keywords: AMPA receptors; KIF1C; actin; cytoskeleton; dendritic spine; intracellular transport; kinesin; microtubule; myosin; myosinV; myosinVI; synaptic plasticity