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Cell. 2016 Jan 14;164(1-2):183-196. doi: 10.1016/j.cell.2015.11.034.

Astrocytes Assemble Thalamocortical Synapses by Bridging NRX1α and NL1 via Hevin.

Author information

1
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710. Electronic address: sandeep.singh@duke.edu.
2
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710.
3
Department of Pediatrics, University of Maryland, School of Medicine, Baltimore, MD 21201.
4
Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710.
5
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710.
6
Biozentrum University of Basel, 4056 Basel, Switzerland.
7
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710; Department of Neurobiology, Duke University Medical Center, Durham, NC 27710; Duke Institute for Brain Sciences (DIBS), Durham, NC 27710.
8
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710; Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710; Department of Neurobiology, Duke University Medical Center, Durham, NC 27710; Duke Institute for Brain Sciences (DIBS), Durham, NC 27710.
9
Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710; Department of Neurobiology, Duke University Medical Center, Durham, NC 27710.
10
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710; Department of Neurobiology, Duke University Medical Center, Durham, NC 27710; Duke Institute for Brain Sciences (DIBS), Durham, NC 27710. Electronic address: cagla.eroglu@dm.duke.edu.

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.

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PMID:
26771491
PMCID:
PMC4715262
DOI:
10.1016/j.cell.2015.11.034
[Indexed for MEDLINE]
Free PMC Article

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