Evidence map›Paper›PMID 42223381›Full record

ArticleThe Journal of cell biology2026

Neuroligin-2 is ubiquitinated by Nedd4l to control developmental astrocyte morphogenesis.

Kristina Sakers, Juan J Ramirez, Nimrod Elazar, Leykashree Nagendren, Erik Soderblom, Cagla Eroglu

Abstract read
In one paragraph

Article in The Journal of cell biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Kristina SakersDepartment of Cell Biology, Duke University Medical Center, Durham, NC, USA.ORCID 0000-0001-8853-053X
Juan J RamirezDepartment of Cell Biology, Duke University Medical Center, Durham, NC, USA.ORCID 0000-0001-5724-6384
Nimrod ElazarDepartment of Cell Biology, Duke University Medical Center, Durham, NC, USA.ORCID 0009-0007-5686-0666
Leykashree NagendrenDepartment of Cell Biology, Duke University Medical Center, Durham, NC, USA.ORCID 0009-0004-5405-7595
Erik SoderblomDepartment of Cell Biology, Duke University Medical Center, Durham, NC, USA.ORCID 0000-0002-6765-1786
Cagla ErogluDepartment of Cell Biology, Duke University Medical Center, Durham, NC, USA.ORCID 0000-0002-7204-0218

Funding

Novel Genetically Encoded Indicators for Interrogating Neuron-Astrocyte Communication Across TimescalesU19NS123719 · NINDS · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI TIAN, LIN · 2021 to 2025
$10.7M
New Proteomic and Genome Engineering Approaches to Decipher Astrocyte Function at SynapsesR01DA047258 · NIDA · DUKE UNIVERSITY · PI EROGLU, CAGLA, SODERLING, SCOTT H · 2018 to 2020
$2.1M
Control of Astrocyte Development and Astrocyte-Synapse InteractionsR01NS102237 · NINDS · DUKE UNIVERSITY · PI EROGLU, CAGLA · 2018 to 2022
$1.9M
Control of Astrocyte Morphogenesis and Synaptogenesis by Astrocytic NeuroliginsF32NS112565 · NINDS · DUKE UNIVERSITY · PI SAKERS, KRISTINA I · 2019 to 2021
$177k
A novel role for astrocyte-secreted synaptogenic factor Hevin/SPARCL1 in microglia-mediated synaptic pruning in response to visual experienceF31NS125985 · NINDS · DUKE UNIVERSITY · PI RAMIREZ, JUAN JOSE · 2022 to 2023
$79k
Life Sciences Research FoundationNIDA NIH HHS R01 DA047258NIH HHS F31NS125985NIH HHS F32 NS112565NIH HHS R01 DA047258NIH HHS R01 NS102237NINDS NIH HHS F31 NS125985NINDS NIH HHS F32 NS112565NINDS NIH HHS R01 NS102237NINDS NIH HHS U19 NS123719The Ruth K. Broad Biomedical Research Foundation
6 · The paper itself

Abstract

Central nervous system astrocytes have an intricate, highly branched morphology. Proper development of perisynaptic astrocyte processes is necessary for tripartite synapse formation and function. However, cellular pathways orchestrating this development are largely unknown. Neuroligins (NLs) 1-3 regulate astrocyte morphogenesis via transcellular adhesions with neuronal neurexins. Here, we found an astrocytic NL2-based mechanism governing morphogenesis. Through structure and function studies, we identified a WW-binding motif within the NL2 intracellular domain required for astrocyte morphogenesis. Using cell-specific in vivo proximity labeling (iBioID), we found that each NL displays distinct protein-protein interactions within astrocytes, distinct from the neuronal NL2-binding partners. From these data, we identified a role for WW domain-containing E3 ubiquitin ligase Nedd4l in astrocyte morphogenesis. Biochemical assays revealed Nedd4l ubiquitinates and stabilizes NL2, and this ubiquitination is required for astrocyte morphogenesis. This study shows that NLs have nonoverlapping roles in controlling astrocyte growth and uncovers a molecular mechanism of how NL2 mediates astrocyte morphogenesis.

Indexed as

AstrocytesCell Adhesion Molecules, NeuronalMorphogenesisNedd4 Ubiquitin Protein LigasesUbiquitinationAnimalsHumansMiceProtein BindingCell Adhesion Molecules, NeuronalNedd4l protein, mouseNedd4 Ubiquitin Protein Ligases

Identifiers

PMID42223381
PMCPMC13276441

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.