# Control of Astrocyte Morphogenesis and Synaptogenesis by Astrocytic Neuroligins

> **NIH NIH F32** · DUKE UNIVERSITY · 2020 · $64,926

## Abstract

Astrocytes are essential for neural circuit assembly and function. Specifically, astrocytes play critical roles in
development of synapses though release of soluble synaptogenic molecules as well as through contact-
dependent mechanisms with neighboring neurons. Astrocyte-synapse interactions are mediated through the
elaborate branching of astrocyte processes, often encompassing tens of thousands of synapses per astrocyte.
Recently, the Eroglu lab discovered a novel contact-dependent interaction regulating both development of
astrocyte morphology and synaptogenesis. This interaction is mediated through astrocytic neuroligins, a family
of cell adhesion molecules previously studied exclusively in neurons. Neuroligins are post-synaptic proteins
that make transcellular connections with pre-synaptic neurexins to regulate synaptogenesis and synaptic
transmission. Interestingly, the Eroglu lab found that astrocytic neuroligins perform distinct functions from
neuronal neuroligins, demonstrating that their expression in astrocytes is functionally significant. Specifically,
this study established that loss of astrocytic neuroligin-2 is sufficient to significantly diminish elaboration of
astrocyte branching and disrupt the excitation/inhibition balance in the mouse cortex. While these findings
highlight a novel player in astrocytic control of morphogenesis and synaptogenesis, the molecular
underpinnings of astrocytic neuroligin interactions remain unexplored. Here, I aim to elucidate the molecular
mechanisms governing astrocytic neuroligin-2 involvement in astrocyte morphogenesis, synapse development
and synaptic physiology. To do so, I will use both in vitro and in vivo manipulation of astrocytic neuroligin-2 to
1) use quantitative proteomics to discover and validate intracellular and extracellular astrocytic neuroligin-2
binding partners critical for regulation of astrocyte morphogenesis and synaptogenesis 2) assess the
sufficiency of astrocytic neuroligin-2 to organize post-synaptic membranes and 3) assess synaptic function in
astrocytic neuroligin-2 null brains. In summary, the data collected in these studies will reveal how astrocytic
neuroligin interactions control development of both astrocytes and synapses and ultimately how these
mechanisms converge to influence synaptic transmission. Neuroligins have been implicated in
neurodevelopmental diseases such as autism and schizophrenia and therefore, it is imperative to understand
the comprehensive functions of neuroligins in all cell types of the brain.

## Key facts

- **NIH application ID:** 9988844
- **Project number:** 5F32NS112565-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Kristina I Sakers
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $64,926
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988844

## Citation

> US National Institutes of Health, RePORTER application 9988844, Control of Astrocyte Morphogenesis and Synaptogenesis by Astrocytic Neuroligins (5F32NS112565-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9988844. Licensed CC0.

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