# FUNCTION AND REGULATION OF APL-1, THE C. ELEGANS HOMOLOGUE TO HUMAN APP

> **NIH NIH R21** · CITY COLLEGE OF NEW YORK · 2020 · $196,250

## Abstract

Li, Christine
Project Summary
Deposition of dense plaques and the presence of neurofibrillary tangles are two postmortem
criteria used in the definitive diagnosis of Alzheimer's disease. The major component of the
dense plaques is a 40-42 amino acid beta-amyloid peptide that is derived from the larger
amyloid precursor protein (APP), a single pass transmembrane domain protein. Mice carrying a
knockout of APP show several behavioral and cognitive defects, which can be rescued by
knockin of full-length APP or only the extracellular domain of APP. However, a family of APP-
related proteins is present in mammals. Knockout of the APP family in mice leads to postnatal
lethality and type II lissencephaly, indicating that the APP family has essential functions during
development. We are interested in studying the function of APP and are approaching this
problem by examining an APP-related gene in a simple model system, the nematode
Caenorhabditis elegans. Knockout of apl-1 leads to larval lethality, which can be rescued by
germline transformation of an apl-1 genomic fragment or a fragment encoding only the
extracellular domain of APL-1. Animals carrying the apl-1(yn5) mutation are viable, produce
high levels of only the APL-1 extracellular domain, and show several phenotypes, including a
slowed development and shortened lifespan. We are specifically interested in the role of sAPL-1
and how its cleavage is regulated. We have developed tools to follow sAPL-1 after its cleavage
at the cell surface, which will allow us to identify the cells to which sAPL-1 binds and the
signaling pathway initiated in these cells. Interfering with α-secretase activity changes overall
levels of APL-1 and its cleavage products; the mechanism underlying these changes will be
examined. Understanding APL-1 function, and particularly the role of sAPL-1, may provide
insights into the function of APP in higher animals, such as man.

## Key facts

- **NIH application ID:** 9985707
- **Project number:** 5R21AG064625-02
- **Recipient organization:** CITY COLLEGE OF NEW YORK
- **Principal Investigator:** CHRISTINE LI
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $196,250
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985707

## Citation

> US National Institutes of Health, RePORTER application 9985707, FUNCTION AND REGULATION OF APL-1, THE C. ELEGANS HOMOLOGUE TO HUMAN APP (5R21AG064625-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9985707. Licensed CC0.

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