# Genetics of secretion in yeast

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $452,332

## Abstract

Project Summary
The cortical endoplasmic reticulum (ER) undergoes autophagic degradation in response to the accumulation of
aggregated proteins within its lumen or in response to starvation. Our studies in yeast have shown that the
cortical ER is remodeled by an actin-dependent mechanism so as to bring elements of ER carrying the
selective autophagy receptor Atg40 into the vicinity of the autophagy machinery near the vacuole. The
segment of ER destined for degradation must be severed from the remainder of the ER network, engulfed by
an autophagosome and delivered to the vacuole for degradation. To identify the components involved in each
step we have conducted a systematic screen for mutants specifically defective in autophagy of the cortical ER.
Here we focus on two key aspects:
The first concerns actin-dependent ER-remodeling. Several lines of evidence suggest that the cortical ER is
tethered to endocytic pits on the plasma membrane as they are internalized by actin polymerization. We will
explore the spatial and temporal relationship between the endocytic pit and the cortical ER during
internalization as well as the role of a putative bridge connecting the two membranes. We will test the role of
the ARP2/3 complex in remodeling the cortical ER as well as the role of a GTPase activating protein, its
substrate and various effectors.
The second focus concerns the role of a putative tether in autophagy of the cortical ER. This tether is a large
protein found at inter-organelle contact sites that is thought to mediate phospholipid transfer. We will determine
which stage of the ER autophagy pathway is affected by its loss. We will establish which contact sites are
involved in autophagy of the cortical ER and will identify the adaptor that links it to these contact sites. Humans
express several isoforms and each is associated with a different disease. We will determine which isoform is
involved in ER autophagy.

## Key facts

- **NIH application ID:** 10440332
- **Project number:** 5R01GM035370-37
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** PETER Jay NOVICK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $452,332
- **Award type:** 5
- **Project period:** 1985-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10440332

## Citation

> US National Institutes of Health, RePORTER application 10440332, Genetics of secretion in yeast (5R01GM035370-37). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10440332. Licensed CC0.

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