Astrocytic neuroligins control astrocyte morphogenesis and synaptogenesis

Jeff A. Stogsdill, Juan Ramirez, Di Liu, Yong Ho Kim, Katherine T. Baldwin, Eray Enustun, Tiffany Ejikeme, Ru-Rong Ji and Cagla Eroglu ()
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Jeff A. Stogsdill: Duke University Medical Center
Juan Ramirez: Duke University Medical Center
Di Liu: Duke University Medical Center
Yong Ho Kim: Duke University Medical Center
Katherine T. Baldwin: Duke University Medical Center
Eray Enustun: Duke University Medical Center
Tiffany Ejikeme: Duke University Medical Center
Ru-Rong Ji: Duke University Medical Center
Cagla Eroglu: Duke University Medical Center

Nature, 2017, vol. 551, issue 7679, 192-197

Abstract: Abstract Astrocytes are complex glial cells with numerous fine cellular processes that infiltrate the neuropil and interact with synapses. The mechanisms that control the establishment of astrocyte morphology are unknown, and it is unclear whether impairing astrocytic infiltration of the neuropil alters synaptic connectivity. Here we show that astrocyte morphogenesis in the mouse cortex depends on direct contact with neuronal processes and occurs in parallel with the growth and activity of synaptic circuits. The neuroligin family cell adhesion proteins NL1, NL2, and NL3, which are expressed by cortical astrocytes, control astrocyte morphogenesis through interactions with neuronal neurexins. Furthermore, in the absence of astrocytic NL2, the formation and function of cortical excitatory synapses are diminished, whereas inhibitory synaptic function is enhanced. Our findings highlight a previously undescribed mechanism of action for neuroligins and link astrocyte morphogenesis to synaptogenesis. Because neuroligin mutations have been implicated in various neurological disorders, these findings also point towards an astrocyte-based mechanism of neural pathology.

Date: 2017
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DOI: 10.1038/nature24638

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