# Elucidating the role of the E3 ubiquitin ligase UBE3B in neuronal activity

> **NIH NIH F31** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $37,674

## Abstract

Project Summary
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects 1 in 54 children and exhibits
significant phenotypic and genetic heterogeneity. Mutations in UBE3B, which encodes an E3 ubiquitin ligase,
have been identified in patients presenting with intellectual disability, lack of speech, and ASD. The specific
mechanism through which disruption of UBE3B, and subsequent dysregulation of its substrates, leads to
neurodevelopmental abnormalities is unknown. Our group has previously shown that a Ube3b constitutive
knockout mouse model exhibits a complete loss of vocalization and defects in nest building, as well as reduced
dendritic complexity, length, and spine density. In this proposal, I will investigate the neuronal function of UBE3B
by characterizing changes in neuronal activity following loss of UBE3B and identifying its neuronal substrates. I
will apply complimentary electrophysiological and biochemical approaches using a brain-specific conditional
Ube3b knockout mouse model (cKOnestin). I will characterize the electrophysiological properties of cortical
neurons from cKOnestin mice, by evaluating their basal properties, including intrinsic excitability and rheobase
current, and both short-term and long-term synaptic plasticity. Furthermore, I will identify the neuronal substrates
of UBE3B through analysis of protein levels, protein-protein interactions, and ubiquitination status. I will also
assess the UBE3B-mediated modifications of substrates, including the site of ubiquitination and the ubiquitin
chain topology. Successful completion of the proposed aims will provide new insights into the interplay of
ubiquitin signaling and neurodevelopment, as well as advance our knowledge of the specific pathogenic
mechanisms underlying neurodevelopmental disorders.
 The exceptional research environment at UT Southwestern Medical Center, combined with the collective
expertise of the mentorship team, will provide excellent training. Goals for this fellowship training include
becoming knowledgeable in the relevant literature and attaining proficiency in both experimental procedures and
communicating scientific information to varied audiences. The skills obtained through these goals will build the
foundation for an independent and successful lead investigator in scientific research.

## Key facts

- **NIH application ID:** 10536505
- **Project number:** 1F31HD110206-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Shayal Vashisth
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $37,674
- **Award type:** 1
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10536505

## Citation

> US National Institutes of Health, RePORTER application 10536505, Elucidating the role of the E3 ubiquitin ligase UBE3B in neuronal activity (1F31HD110206-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10536505. Licensed CC0.

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