# Functional role of Sec20, a BH3 and Secretory (Sec) domain protein, in neurons and its relevance to a motor neuron disease in Drosophila

> **NIH NIH RF1** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2023 · $1,310,312

## Abstract

Contact PD/PI: BHAT, KRISHNA MOORTHI
 This proposal examines the functional role of Sec20, a BH3 and Secretory (Sec) domain protein, in
neurons and its relevance to a motor neuron disease using Drosophila. It also examines the interaction
between sec20 and GGGGCC (G4C2) repeats of the gene C9orf72 (Chromosome9 open reading frame), a well-
known mutation that causes Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia (FTD) in
humans. ALS-FTD are two progressive, adult-onset neurodegenerative diseases, often occurring together. The
particular focus of this proposal is neuronal loss and mitochondrial and autophagy defects in the brain.
Dysfunctional mitochondria and autophagic failures have emerged as important factors in
neurodegenerative diseases. They may actively mediate these diseases or exacerbate them.
 sec20 is the ortholog of vertebrate Bnip1 gene, which is a member of the Bcl2 interacting protein
family. Bnip1 has been tentatively identified as a risk factor for ALS and FTD in humans. We found that loss
of function for sec20 in the CNS in Drosophila caused severe motor neuron disease and death. There
was neuronal loss, mitochondrial dysfunction and autophagic failures in these flies. The disease and these
molecular features had similarities to the motor deficits disease caused by the expression of G4C2 repeats. The
phenotypes caused by the G4C2 repeats were upstream of sec20 in flies as well as in humans.
 Thus, our specific aims are: 1) Determine the molecular basis for the loss of motor neurons in sec20
mutant flies, 2) Determine if defective mitophagy and autophagy in sec20 mutants contribute to the
disease, and 3) Delineate the interaction between sec20 and the c9orf72-G4C2-R in the CNS.
 In Drosophila, we go from phenotypes to genes and then molecular underpinnings. There is always a
bottom line with this system. Our aims investigate the basics of the phenotypes caused by these
genes/mutations. These studies will help understand the function of Sec20 in the CNS and how it relates to
G4C2 repeats in the biology and in the diseases of the brain.
Project Summary/Abstract Page 6

## Key facts

- **NIH application ID:** 11126452
- **Project number:** 7RF1NS131315-02
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** KRISHNA MOORTHI BHAT
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1,310,312
- **Award type:** 7
- **Project period:** 2023-04-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11126452

## Citation

> US National Institutes of Health, RePORTER application 11126452, Functional role of Sec20, a BH3 and Secretory (Sec) domain protein, in neurons and its relevance to a motor neuron disease in Drosophila (7RF1NS131315-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11126452. Licensed CC0.

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