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Astrocytes assemble thalamocortical synapses by bridging NRX1α and NL1 via Hevin

Singh, Sandeep K., Stogsdill, Jeff A., Pulimood, Nisha S., Dingsdale, Hayley, Kim, Yong Ho, Pilaz, Louis-Jan, Kim, Il Hwan, Manhaes, Alex C., Rodrigues, Wandilson S., Pamukcu, Arin, Enustun, Eray, Ertuz, Zeynep, Scheiffele, Peter, Soderling, Scott H., Silver, Debra L., Ji, Ru-Rong, Medina, Alexandre E. and Eroglu, Cagla 2016. Astrocytes assemble thalamocortical synapses by bridging NRX1α and NL1 via Hevin. Cell 164 (1-2) , pp. 183-196. 10.1016/j.cell.2015.11.034

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Abstract

Proper establishment of synapses is critical for constructing functional circuits. Interactions between presynaptic neurexins and postsynaptic neuroligins coordinate the formation of synaptic adhesions. An isoform code determines the direct interactions of neurexins and neuroligins across the synapse. However, whether extracellular linker proteins can expand such a code is unknown. Using a combination of in vitro and in vivo approaches, we found that hevin, an astrocyte-secreted synaptogenic protein, assembles glutamatergic synapses by bridging neurexin-1alpha and neuroligin-1B, two isoforms that do not interact with each other. Bridging of neurexin-1alpha and neuroligin-1B via hevin is critical for the formation and plasticity of thalamocortical connections in the developing visual cortex. These results show that astrocytes promote the formation of synapses by modulating neurexin/neuroligin adhesions through hevin secretion. Our findings also provide an important mechanistic insight into how mutations in these genes may lead to circuit dysfunction in diseases such as autism.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: Elsevier
ISSN: 0092-8674
Date of Acceptance: 10 November 2015
Last Modified: 15 Apr 2019 11:01
URI: http://orca.cf.ac.uk/id/eprint/120673

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