# Formation of the Regulated Secretory Pathway: a View from the Cytosol

> **NIH NIH R01** · UNIVERSITY OF DENVER (COLORADO SEMINARY) · 2021 · $292,565

## Abstract

Abstract
The ability to release signaling molecules, such as peptide hormones, neuropeptides, and many growth
factors, in response to an appropriate extracellular stimulus, is central to physiology, behavior, and
development. The secretory vesicles mediating this regulated secretion are called large dense core vesicles
(LDCVs). They bud from the trans-Golgi network (TGN) where their soluble cargo aggregates to form a dense
core, but the cellular mechanisms, and in particular, the cytosolic machinery that produces these secretory
vesicles are still not well understood. Recent published studies in C. Elegans have identified HID-1 as a
cytosolic factor involved in neuropeptide sorting, but its function remains unknown. HID-1 is a peripheral
membrane protein associated with the TGN and its expression is restricted to neuroendocrine cells, suggesting
that it might contribute to LDCV biogenesis. Our preliminary loss-of-function experiments with rat
neuroendocrine HID-1 knockout (KO) cells generated by genome-editing have confirmed that HID-1 is indeed
required for mammalian neuroendocrine secretion. We will now 1) determine how HID-1 contributes to LDCV
formation using a combination of biochemical and imaging assays, 2) establish how HID-1 targets specifically
to the TGN, and 3) identify the mechanism regulating the reversible binding of HID-1 to the TGN and assess its
significance for LDCV formation. These studies will provide invaluable information about the cell biology and
biochemistry of a novel peripheral membrane protein involved in membrane trafficking with important
implications for our understanding of neuroendocrine secretion.

## Key facts

- **NIH application ID:** 10237997
- **Project number:** 5R01GM124035-05
- **Recipient organization:** UNIVERSITY OF DENVER (COLORADO SEMINARY)
- **Principal Investigator:** Cedric Stephane Asensio
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $292,565
- **Award type:** 5
- **Project period:** 2017-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10237997

## Citation

> US National Institutes of Health, RePORTER application 10237997, Formation of the Regulated Secretory Pathway: a View from the Cytosol (5R01GM124035-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10237997. Licensed CC0.

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