Calsyntenin-1 Regulates Targeting of Dendritic NMDA Receptors and Dendritic Spine Maturation in CA1 Hippocampal Pyramidal Cells during Postnatal Development

Autor: Martin Steuble, Urs Gerber, Peter Sonderegger, Clara Orlando, Alexander Akhmedov, Olivier Raineteau, Vincent Pernet, Jeanne Ster, Tu-My Diep
Přispěvatelé: University of Zurich, Gerber, Urs
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: Journal of Neuroscience
Popis: 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. © 2014 the authors.
Databáze: OpenAIRE