# GENETICS OF ENDOCYTIC TRAFFICKING IN THE DROSOPHILA EYE

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $410,000

## Abstract

Neurons in adults are essentially irreplaceable and especially vulnerable to the
accumulation of protein aggregates, dysfunctional mitochondria, and similarly distractive
agents. The most important pathway available to neurons to limit such damage is
autophagy. This pathway, initially described in the context of the mTor-regulated
starvation-induced metabolic rescue pathway in yeast and mammalian cells, is initiated
by the formation of an isolation membrane followed by its expansion, the engulfment of
cytoplasmic content into a closed autophagosome and its fusion to the lysosomes and
degradation of autophagosomal content. Beyond its importance in the starvation
response, starvation and mTor-independent autophagy is increasingly recognized as an
important quality control mechanism that reduces degeneration of neurons and
photoreceptor cells and has implications for cancer and infectious diseases. Therefore,
the distinct cellular signaling pathways that adjust the rate of autophagy to the cell’s
physiology are important to understand. Because excessive autophagy is lethal to cells,
the different signaling pathways inducing autophagy must be careful coordinated and
calibrated. For one such pathway, the Acinus protein is as a critical regulator. The
Acinus protein integrates signals from multiple pathways to modulate the function of core
autophagy proteins and stimulate the induction of starvation-independent autophagy.
This grant aims to understand the molecular mechanisms that regulate the levels of Acn
protein and its activity. For this purpose, in Aim 1, we propose to define upstream
regulators of Acinus including the phosphatases and kinases responsible for regulating
its activity and explore their potential as possible drug targets. In Aim 2, we will analyze
the mechanistic link between Acinus and its effector Atg1, the master regulatory kinase
of the autophagy pathway. In Aim 3, we will explore physiological consequences of
disrupting the Acn-Atg1 signaling module in the context of visual system.

## Key facts

- **NIH application ID:** 10929402
- **Project number:** 5R01EY010199-29
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Helmut J Kramer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $410,000
- **Award type:** 5
- **Project period:** 2023-09-30 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10929402

## Citation

> US National Institutes of Health, RePORTER application 10929402, GENETICS OF ENDOCYTIC TRAFFICKING IN THE DROSOPHILA EYE (5R01EY010199-29). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10929402. Licensed CC0.

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