title: Calsyntenin-1 regulates targeting of dendritic NMDA receptors and dendritic spine maturation in CA1 hippocampal pyramidal cells during postnatal development.
abstract: Calsyntenin-1 is a transmembrane cargo-docking protein important for kinesin-1-mediated fast transport of membrane-bound organelles that exhibits peak expression levels at postnatal day 7. However, its neuronal function during postnatal development remains unknown. We generated a knock-out mouse to characterize calsyntenin-1 function in juvenile mice. In the absence of calsyntenin-1, synaptic transmission was depressed. To address the mechanism, evoked EPSPs were analyzed revealing a greater proportion of synaptic GluN2B subunit-containing receptors typical for less mature synapses. This imbalance was due to a disruption in calsyntenin-1-mediated dendritic transport of NMDA receptor subunits. As a consequence of increased expression of GluN2B subunits, NMDA receptor-dependent LTP was enhanced at Schaffer collateral-CA1 pyramidal cell synapses. Interestingly, these defects were accompanied by a decrease in dendritic arborization and increased proportions of immature filopodia-like dendritic protrusions at the expense of thin-type dendritic spines in CA1 pyramidal cells. Thus, these results highlight a key role for calsyntenin-1 in the transport of NMDA receptors to synaptic targets, which is necessary for the maturation of neuronal circuits during early development.
authors: Brain Research Institute and.
authors: Jeanne
authors: J
authors: Ster
authors: Department of Biochemistry, University of Zurich, CH-8057 Zurich, Switzerland.
authors: Martin
authors: M
authors: Steuble
authors: Brain Research Institute and.
authors: Clara
authors: C
authors: Orlando
authors: Department of Biochemistry, University of Zurich, CH-8057 Zurich, Switzerland.
authors: Tu-My
authors: TM
authors: Diep
authors: Department of Biochemistry, University of Zurich, CH-8057 Zurich, Switzerland.
authors: Alexander
authors: A
authors: Akhmedov
authors: Brain Research Institute and.
authors: Olivier
authors: O
authors: Raineteau
authors: Brain Research Institute and.
authors: Vincent
authors: V
authors: Pernet
authors: Department of Biochemistry, University of Zurich, CH-8057 Zurich, Switzerland.
authors: Peter
authors: P
authors: Sonderegger
authors: Brain Research Institute and gerber@hifo.uzh.ch.
authors: Urs
authors: U
authors: Gerber
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism*; D049229:Dendritic Spines / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D017966:Pyramidal Cells / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013569:Synapses / Q000502:physiology
chemical_list: D002135:Calcium-Binding Proteins; C503227:Clstn1 protein, mouse; D016194:Receptors, N-Methyl-D-Aspartate
keywords: CA1 pyramidal cells; GluN2B subunit; NMDA receptors; calsyntenin-1; receptor targeting; spine maturation