Journal Article

Astrocytic neuroligins control astrocyte morphogenesis and synaptogenesis

Ramirez, Juan, Stogsdill, Jeff A., Baldwin, Katherine T., Enustun, Eray, Ji, Ru-Rong, Ejikeme, Tiffany, Eroglu, Cagla, Liu, Di, Kim, Yong Ho

2017

Overview

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. Astrocyte morphogenesis depends on interactions between astrocytic neuroligins and neuronal neurexins. Neuroligins adjust their astrocytes It has long been known that astrocytes maintain an intimate relationship with neurons and can influence synapses with their complex morphology and close physical interactions. However, the molecular means by which the astrocyte initiates and maintains the required morphology to participate in synaptic regulation are not well known. Here, Cagla Eroglu and colleagues report that neuroligins—a family of cell adhesion molecules—expressed by astrocytes can bind to neurexins expressed on neurons to regulate astrocyte morphogenesis and modulate synaptic density and function.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/106 / 13/31 / 13/51 / 13/89 / 14/1 / 14/19 / 14/32 / 14/35 / 38/109 / 38/77 / 38/88 / 631/378/2571/219 / 631/378/2571/2577 / 631/378/2596/1308 / 631/80/79 / 64/60 / 82/80 / 82/83 / Analysis / Animals / Astrocytes / Astrocytes - cytology / Astrocytes - metabolism / Cell adhesion / Cell adhesion molecules / Cell Adhesion Molecules, Neuronal - metabolism / Cell Shape - physiology / Cerebral Cortex - cytology / Cerebral Cortex - metabolism / Cortex / Gene expression / Glial cells / Humanities and Social Sciences / Identification and classification / Infiltration / Membrane proteins / Mice / Morphogenesis / Morphology / multidisciplinary / Mutation / Neural Cell Adhesion Molecules - metabolism / Neural Inhibition / Neural networks / Neurological diseases / Neuronal-glial interactions / Neurons / Neurophysiology / Neuropil / Observations / Physiological aspects / Proteins / Receptors, Cell Surface - metabolism / Science / Synapses / Synapses - metabolism / Synaptogenesis