# Project 3: Understanding the Role of FSHR Oligomerization and Trafficking in Transducing Age-dependent Changes in FSH Glycoforms

> **NIH NIH P01** · WICHITA STATE UNIVERSITY · 2024 · $232,797

## Abstract

Project Summary/Abstract – Project 3(Jonas)
The goal of this project is to understand how age-dependent changes in follicle stimulating hormone (FSH)
glycosylation are transduced by its G protein-coupled receptor, FSH receptor (FSHR). Studies by Project
4(Bousfield) reported age-dependent changes in the glycosylation pattern of FSH; with a reduction in partially
glycosylated FSH (FSH18/21) and an increase in fully glycosylated FSH (FSH24) observed with aging. These
modifications in FSH glycosylation have significant functional impact, with FSH18/21 displaying faster binding
and more potent signal activation than FSH24. However, it remains unknown how aging and folliculogenesis-
dependent changes in the cellular microenvironment impacts FSH glycoform-dependent FSHR modulation,
which will be addressed by this project. Two important mechanisms that modulate G protein-coupled receptor
function is the formation of GPCR dimers and oligomers, and receptor trafficking. Our recently published
studies suggest that FSH glycoforms differentially modulate FSHR oligomerization, with impact on cAMP
signaling. Moreover, our pilot data suggests that FSH glycoforms may differentially control FSHR
endocytosis. The overarching aim of this project is therefore to understand how FSH glycoforms regulate
FSHR oligomerization and trafficking in primary granulosa cells, during folliculogenesis and aging. The
working hypothesis is that FSH glycoform-specific modulation of FSHR oligomerization results in distinct
trafficking and signaling signatures, with defined functional consequences. The Specific Aims are: 1.
Assessing FSH glycoform-specific regulation of FSHR complexes in granulosa cells of young and
reproductively advanced mice. Our working hypothesis is that FSH glycoform modulation of FSHR
homomers and signal output will be differentially regulated by aging and stage of follicle development. We
will utilize an N terminal tagged FLAG-FSHR knock in mouse to test this hypothesis. 2. Determining the role
of endosomal FSHR in directing FSH glycoform-dependent functional selectivity. Our working
hypothesis is that FSH glycoform-dependent FSHR internalization directs functional selectivity in signal
output and adapter protein binding. We will utilize primary granulosa cells and multicolor fluorescent confocal
and TIRF microscopy to determine the spatial-temporal nature of FSH glycoform and aging modulated FSHR
trafficking. 3. Understanding how FSH glycoforms modulate FSHR interactions with modulatory and
adapter proteins. Our working hypothesis is that FSH glycoforms drive functional selectivity through
differential recruitment of signaling machinery and modulatory proteins. A FSHR pulldown strategy and LC-
MS/MS will determine the FSH glycoform-dependent FSHR interactome. The function of FSHR- interacting
proteins will be assessed by siRNA/over-expression, and age-dependent modulation determined. The project
outcomes will elucidate how age-dependent regulation of FSH glyc...

## Key facts

- **NIH application ID:** 10848246
- **Project number:** 5P01AG029531-12
- **Recipient organization:** WICHITA STATE UNIVERSITY
- **Principal Investigator:** KIM CAROL JONAS
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $232,797
- **Award type:** 5
- **Project period:** 2009-04-15 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10848246

## Citation

> US National Institutes of Health, RePORTER application 10848246, Project 3: Understanding the Role of FSHR Oligomerization and Trafficking in Transducing Age-dependent Changes in FSH Glycoforms (5P01AG029531-12). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10848246. Licensed CC0.

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