# Genetic analysis of regulated exocytosis during Drosophila development

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $296,393

## Abstract

ABSTRACT
Regulated exocytosis is a fundamental and critical cell biological process during which specialized
secretory cells release cargo proteins in response to specific stimuli. This process has broad
implications for human health, as dysfunction of regulated exocytosis results in many disorders,
including the conspicuous example of impaired insulin secretion in diabetes mellitus. Developmental
growth disorders, asthma, and thyroid dysfunction are also caused by abnormalities in regulated
exocytosis. However, despite this critical importance for human health, major steps in the regulated
exocytosis pathway remain poorly understood. There is a particular lack of understanding of
mechanisms regulating maturation of cargo-carrying secretory granules, a step that is critical to render
these specialized organelles competent for exocytosis and to ensure that the secreted cargo is
biologically active. Progress has been inhibited largely because of a lack of a genetic context in which
to study secretory granule maturation; previous studies have relied largely on visual observations via
electron microscopy (EM) and biochemical separation and purification of secretory granules.
Importantly, we have identified a novel, highly-conserved regulator of secretory granule maturation,
named hobbit, with associated severe defects in regulated exocytosis in both neuroendocrine and
epithelial cells. The long-term goal of this project is to identify and characterize novel proteins, including
hobbit, that are required for regulated exocytosis. The overall objective of this application is to
understand the function of hobbit and hobbit-dependent granule maturation during regulated
exocytosis. Our central hypothesis is that hobbit, a novel component of the regulated exocytosis
pathway, cooperates with the ESCRT machinery and Rab proteins to regulate the progression of
secretory granules through the process of maturation. We intend to test the central hypothesis and
accomplish the overall objective of this proposal by pursuing the following two specific aims: 1) What is
the function of hobbit in regulated exocytosis; and 2) Define the molecular pathway in which hobbit
functions. The focus of Aim 1 is to uncover the function of hobbit in secretory granule maturation. The
focus of Aim 2 is to identify critical members of the hobbit-dependent secretory pathway, and to identify
other new regulators of regulated exocytosis. Our contribution is significant because we have identified
a previously uncharacterized regulator of secretory granule maturation, allowing us to genetically
dissect the molecular pathway regulating this process. We expect this work to provide new mechanistic
insights into the regulated exocytosis pathway, which will have important implications for our
understanding of the etiology of secretion-related diseases, including diabetes.

## Key facts

- **NIH application ID:** 9959444
- **Project number:** 5R01GM123204-04
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** ARASH BASHIRULLAH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $296,393
- **Award type:** 5
- **Project period:** 2017-08-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9959444

## Citation

> US National Institutes of Health, RePORTER application 9959444, Genetic analysis of regulated exocytosis during Drosophila development (5R01GM123204-04). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9959444. Licensed CC0.

---

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