Netrin-G/NGL complexes encode functional synaptic diversification Journal Article

Author(s): Matsukawa, Hiroshi; Akiyoshi-Nishimura, Sachiko; Zhang, Qi; Luján, Rafael; Yamaguchi, Kazuhiko; Goto, Hiromichi; Yaguchi, Kunio; Hashikawa, Tsutomu; Sano, Chie; Shigemoto, Ryuichi; Nakashiba, Toshiaki; Itohara, Shigeyoshi
Article Title: Netrin-G/NGL complexes encode functional synaptic diversification
Affiliation IST Austria
Abstract: Synaptic cell adhesion molecules are increasingly gaining attention for conferring specific properties to individual synapses. Netrin-G1 and netrin-G2 are trans-synaptic adhesion molecules that distribute on distinct axons, and their presence restricts the expression of their cognate receptors, NGL1 and NGL2, respectively, to specific subdendritic segments of target neurons. However, the neural circuits and functional roles of netrin-G isoform complexes remain unclear. Here, we use netrin-G-KO and NGL-KO mice to reveal that netrin-G1/NGL1 and netrin-G2/NGL2 interactions specify excitatory synapses in independent hippocampal pathways. In the hippocampal CA1 area, netrin-G1/NGL1 and netrin-G2/NGL2 were expressed in the temporoammonic and Schaffer collateral pathways, respectively. The lack of presynaptic netrin-Gs led to the dispersion of NGLs from postsynaptic membranes. In accord, netrin-G mutant synapses displayed opposing phenotypes in long-term and short-term plasticity through discrete biochemical pathways. The plasticity phenotypes in netrin-G-KOs were phenocopied in NGL-KOs, with a corresponding loss of netrin-Gs from presynaptic membranes. Our findings show that netrin-G/NGL interactions differentially control synaptic plasticity in distinct circuits via retrograde signaling mechanisms and explain how synaptic inputs are diversified to control neuronal activity.
Keywords: Mice; Excitatory synapse; Netrin-G1; Netrin-G2; Pathway specificity; Trans-synaptic adhesion molecule
Journal Title: Journal of Neuroscience
Volume: 34
Issue 47
ISSN: 1529-2401
Publisher: Society for Neuroscience  
Date Published: 2014-01-01
Start Page: 15779
End Page: 15792
DOI: 10.1523/JNEUROSCI.1141-14.2014
Open access: no