# Functional mechanisms underlying Dystroglycan-dependent and independent roles of protein O-mannosylation in the nervous system

> **NIH NIH R01** · TEXAS A&M AGRILIFE RESEARCH · 2020 · $311,261

## Abstract

The main objective of this project is to elucidate functional mechanisms underlying regulation of the
nervous system by protein O-mannosylation (POM). POM is an essential type of O-glycosylation that has a
profound effect on the development and physiology in a broad range of animals, from Drosophila to
humans. Although the spectrum of biological functions affected by POM is wide, so far the only well-studied
target of POM is Dystroglycan (Dg). Defects in POM modifications of Dg result in severe muscular
dystrophies called dystroglycanopathies. Pathomechanisms associated with POM defects are complex and
remain poorly understood, particularly in the nervous system. Recent studies suggested that POM
modification affects functions of many proteins, which contributes to pathogenic mechanisms of
dystroglycanopathies. However, functions of POM on proteins besides Dg are largely unknown. The
complexity of glycosylation and limitations of in vivo approaches create significant challenges for studying
POM in mammalian organisms. Here we propose a multidisciplinary project that uses advantages of
Drosophila model, including powerful arsenal of genetic approaches, simplified glycosylation and
experimental amenability of POM and Dg mutants, to elucidate molecular and cellular mechanisms of Dg-
dependent and Dg-independent functions of POM, with the focus on the nervous system and
neuromuscular development and physiology. Our preliminary studies suggested that Receptor Protein
Tyrosine Phosphatases (RPTPs) are functionally important POM targets and revealed that POM regulates
coordinated muscle contractions by affecting communication between sensory neurons and the CNS. We
will capitalize on these results while focusing on three specific aims: (1) To analyze the role of POM in
regulation of sensory neurons and coordinated muscle contractions. Using live imaging techniques
combined with genetic and neurobiological approaches, we will comprehensively investigate the role of
POM in communication between sensory neurons, CNS cells and muscles. (2) To investigate the effect of
POM on RPTP function. Using in vivo and in vitro approaches, we will investigate how POM affects
functions RPTPs at molecular, cellular, and organismal levels. (3) To reveal new molecular targets of POM
and elucidate their function in the nervous system. We will use glycoproteomic approaches to identify
proteins with POM modifications. We will analyze functions of POM on novel targets in vivo, focusing on
proteins that function in the nervous system. We anticipate that this project will establish new paradigms of
POM-mediated regulation of the nervous system and will elucidate new evolutionarily conserved, Dg-
dependent and independent mechanisms of POM functions, which will shed light on pathomechanisms of
human diseases associated with POM abnormalities.

## Key facts

- **NIH application ID:** 9963424
- **Project number:** 5R01NS099409-04
- **Recipient organization:** TEXAS A&M AGRILIFE RESEARCH
- **Principal Investigator:** VLADISLAV M PANIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $311,261
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9963424

## Citation

> US National Institutes of Health, RePORTER application 9963424, Functional mechanisms underlying Dystroglycan-dependent and independent roles of protein O-mannosylation in the nervous system (5R01NS099409-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9963424. Licensed CC0.

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