An important focus of our research is the investigation of endoplasmic reticulum (ER)-associated glycosylation pathways and the biological function of specialized glycosyltransferases.

ER Glycosylation Pathways

The initial steps of N-glycosylation occur in the ER before further maturation in the Golgi apparatus. Our group previously investigated PMM2 congenital disorders of glycosylation (CDG), which impair the biosynthesis of the mannose donor GDP-mannose and thereby disrupt ER glycosylation processes (Thiesler et al., 2016).

In contrast to classical N-glycosylation, two ER-restricted modifications are not further elongated within the Golgi apparatus:

• C-mannosylation
• TMEM260-dependent O-mannosylation

C-Mannosyltransferases and Novel Glycoproteins

The discovery of the DPY19 family as C-mannosyltransferases represented an important milestone in the field. In humans, four homologs exist (DPY19L1–L4), with DPY19L1 and DPY19L3 functioning as active enzymes (Shcherbakova et al., 2017).

Our research aims to identify and characterize proteins carrying these specialized glycosylation modifications.

Examples include:

• Identification of C-mannosylated ADAMTS16, a protein involved in eye development (Cirksena et al., 2021)
• Development of lectin-based enrichment strategies for the detection of C- and O-mannosylated peptides (Hütte et al., 2022)

Functional and Translational Research

The biological role of C-mannosylation remains largely unknown. To address this question, we combine:

• Advanced glycoproteomics
• Glycobiology
• Stem cell-based model systems
• Functional cell biology approaches

Our goal is to better understand how ER-associated glycosylation regulates protein function, cellular development, and disease mechanisms.