# Determining the localization and function of schizophrenia-linked protein tSNARE1b

> **NIH NIH F31** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $33,771

## Abstract

ABSTRACT
Schizophrenia is a polygenic neuropsychiatric disorder characterized by delusions and
hallucinations, which lacks effective, targeted therapies. Recently, the largest genome wide
association study on schizophrenia to date identified 108 loci as associated with the occurrence
of schizophrenia. The fifth most significant hit mapped to a locus containing the gene TSNARE1,
which encodes the protein t-SNARE domain containing 1 (tSNARE1). tSNARE1 has two isoforms,
which contain a N-terminal c-Myb DNA binding domain and a C-terminal Qa SNARE domain.
Rare variant mutations that were identified from patients with either schizophrenia or autism
spectrum disorder suggest the SNARE domain is critical for its function. Unlike canonical Qa
SNARE proteins, the primary neuronal isoform, tSNARE1b, lacks a transmembrane domain as
well as any other predicted site for membrane attachment, which is necessary for membrane
fusion. Therefore, my central hypothesis is that tSNARE1b acts as an inhibitory SNARE (i-
SNARE) of certain membrane trafficking events. To test this hypothesis, I will first determine to
which compartments tSNARE1b localizes within the endosomal and autophagy networks by
performing high resolution, live-cell confocal microscopy of tSNARE1b-GFP and spectrally
distinct markers of the compartments. I will then determine the effect of tSNARE1b on the
intersection of membrane trafficking between late endosomes, lysosomes, and autophagosomes
with three-color, live-cell imaging. Understanding the cellular and physiological role of tSNARE1b
is necessary towards understanding how its dysfunction may contribute to schizophrenia and
other neuropsychiatric disorders. Therefore, we will repeat the above experiments with the rare
variants of tSNARE1b to determine how these mutations disrupt membrane trafficking at the
intersections of endocytosis and autophagy. Finally, we will collaborate with core facilities to
generate and characterize a knock-in mouse model overexpressing TSNARE1 or a rare variant
to assess its effects on behavior and neuronal connectivity and morphology.

## Key facts

- **NIH application ID:** 10006860
- **Project number:** 5F31MH116576-03
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Melissa Plooster
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $33,771
- **Award type:** 5
- **Project period:** 2018-09-15 → 2021-09-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10006860

## Citation

> US National Institutes of Health, RePORTER application 10006860, Determining the localization and function of schizophrenia-linked protein tSNARE1b (5F31MH116576-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10006860. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*