About

Michael Scott Boyce is a Principal Investigator in the field of Biochemistry at Duke University. His research focuses on cell signaling through O-linked glycosylation, a biochemical process that modifies proteins and influences cellular communication. He is involved in a research project funded by the National Institutes of Health, which is administered by the Biochemistry department at Duke. The project is scheduled to run from April 1, 2026, to March 31, 2031. This work highlights his expertise in the molecular mechanisms underlying cell signaling pathways and the role of glycosylation in these processes.

Research topics

• Political Science
• Physics
• Engineering
• Materials science
• Chemistry
• Engineering ethics
• Nanotechnology
• Business
• Biology
• Anatomy
• Public relations
• Optics
• Medical education
• Medicine

Selected publications

• Dynamic regulation of the COPII interactome and collagen trafficking by site-specific glycosylation of Sec24D

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-06-13 · 1 citations

  preprintSenior authorCorresponding

  Summary Coat protein complex II (COPII) mediates anterograde trafficking from the endoplasmic reticulum (ER). While the core COPII machinery is well-characterized, how cells regulate COPII to accommodate large cargoes, including collagens, remains incompletely understood. Here, we show that the cargo-selecting COPII subunit Sec24D is modified by site-specific O-linked β- N -acetylglucosamine (O-GlcNAc) in its N-terminal intrinsically disordered region upon induction of collagen transport. These glycosylations are required for collagen trafficking in human cells and developing zebrafish. Crosslinking proteomics demonstrated that each O-GlcNAcylation influences the Sec24D interactome in a distinct way, revealing novel mediators of COPII function. In particular, Sec24D glycosylation is required for its interaction with myoferlin, which unexpectedly facilitates fusion of ER exit sites (ERES) and the ER-Golgi intermediate compartment (ERGIC) to enable collagen transport. Our results establish Sec24D O-GlcNAcylation as a dynamic regulator of COPII protein-protein interactions and collagen trafficking and identify myoferlin as a novel mediator of this process.

  PublisherDOI

• Dynamic regulation of Sec24C by phosphorylation and O-GlcNAcylation during cell cycle progression

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-02-14 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Abstract During mitosis, eukaryotic cells cease anterograde trafficking from the endoplasmic reticulum (ER) towards the Golgi. This cessation corresponds with the dispersal of the COPII transport protein, Sec24C, from juxtanuclear ER exit sites (ERES) into a diffusely cytosolic pool. Redistribution of Sec24 paralogs and other core COPII proteins may underlie the mitotic pause in secretion and may be required for the equal inheritance of endomembrane organelles and machinery by both daughter cells. Therefore, it is important to understand the mechanisms governing the mitotic relocalization of COPII components. Here, we explore the role of post-translational modifications (PTMs) of the model COPII protein Sec24C in this phenotypic switch during mitosis. In interphase, Sec24C is modified by O-linked β- N -acetylglucosamine (O-GlcNAc), and we show that this glycan is rapidly removed upon mitotic entry, influencing the timing of Sec24C dispersal. Additionally, we identify novel, cell cycle phase-enriched phosphorylation events on Sec24C, including phosphosites that regulate the stability and localization of the protein, providing the first systematic characterization of dynamic PTMs on any Sec24 protein. Together, our data support the hypothesis that phosphorylation and glycosylation of Sec24C act in concert to induce rapid dispersal upon mitotic entry and may promote equal partitioning of the endomembrane system to daughter cells after division.

  PublisherDOI

• Evidence for functional regulation of the KLHL3/WNK pathway by O-GlcNAcylation

  Glycobiology · 2025-08-11 · 1 citations

  articleOpen accessSenior author

  The 42-member Kelch-like (KLHL) protein family are adaptors for ubiquitin E3 ligase complexes, governing the stability of a wide range of substrates. KLHL proteins are critical for maintaining proteostasis in a variety of tissues and are mutated in human diseases, including cancer, neurodegeneration, and familial hyperkalemic hypertension. However, the regulation of KLHL proteins remains incompletely understood. Previously, we reported that two KLHL family members, KEAP1 and gigaxonin, are regulated by O-linked β-N-acetylglucosamine (O-GlcNAc), an intracellular form of glycosylation. Interestingly, some ubiquitination targets of KEAP1 and gigaxonin are themselves also O-GlcNAcylated, suggesting that multi-level control by this post-translational modification may influence many KLHL pathways. To test this hypothesis, we examined KLHL3, which ubiquitinates with-no-lysine (WNK) kinases to modulate downstream ion channel activity. Our biochemical and glycoproteomic data demonstrate that human KLHL3 and all four WNK kinases (WNK1-4) are O-GlcNAcylated. Moreover, our results suggest that O-GlcNAcylation affects WNK4 function in both osmolarity control and ferroptosis, with potential implications ranging from blood pressure regulation to neuronal health and survival. This work demonstrates the functional regulation of the KLHL3/WNK axis by O-GlcNAcylation and supports a broader model of O-GlcNAc serving as a general regulator of KLHL signaling and proteostasis.

  PublisherOA PDFDOI

• Dynamic O-GlcNAcylation of Sec23-interacting protein regulates COPII function

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-20

  preprintOpen accessSenior authorCorresponding

  Abstract About one-third of the eukaryotic proteome transits the secretory pathway to reach its correct cellular or extracellular destination. At the earliest stage, transport from the endoplasmic reticulum (ER) to the ER-Golgi intermediate compartment (ERGIC) or Golgi apparatus is mediated by coat protein complex II (COPII). COPII coats consist of inner and outer layers formed by Sec23–Sec24 heterodimers and Sec13–Sec31 heterotetramers, respectively, which initially assemble at ER exit sites (ERES) to form transport carriers. Sec23-interacting protein (Sec23IP) links the inner and outer coats through its interactions with both Sec23A and Sec31A, positioning it as a key potential regulator of COPII function. However, the mechanisms controlling Sec23IP activity remain poorly understood. Here, we investigate how physiological stimuli regulate COPII function through the dynamic modification of Sec23IP by O-linked β- N -acetylglucosamine (O-GlcNAc), a reversible, intracellular form of glycosylation. We first validated Sec23IP as a bona fide O-GlcNAcylated protein. Rescue experiments in Sec23IP knockout cells with a nearly unglycosylatable mutant protein demonstrated the essential role of O-GlcNAcylation in the intrinsically disordered domain in protein transport and in recruiting Sec31A to ERES. Moreover, O-GlcNAcylation of Sec23IP increased during protein transport, coinciding with a reduction in its interaction with Sec31A. These results indicate that distinct site-specific O-GlcNAcylation of Sec23IP spatiotemporally modulates its association with Sec31A to fine-tune ERES recruitment and COPII assembly/disassembly. Our work provides new insight into Sec23IP regulation and suggests that O-GlcNAc on other COPII proteins may govern carrier formation, uncoating, and transport.

  PublisherDOI

• Dynamic regulation of Sec24C by phosphorylation and O-GlcNAcylation during cell cycle progression

  Journal of Biological Chemistry · 2025-07-03 · 2 citations

  articleOpen accessSenior author

  During mitosis, eukaryotic cells cease anterograde trafficking from the endoplasmic reticulum (ER) toward the Golgi. This cessation corresponds with the dispersal of the COPII transport protein, Sec24C, from juxtanuclear ER exit sites (ERES) into a diffusely cytosolic pool. Redistribution of Sec24 paralogs and other core COPII proteins may underlie the mitotic pause in secretion and may be required for the equal inheritance of endomembrane organelles and machinery by both daughter cells. Therefore, it is important to understand the mechanisms governing the mitotic relocalization of COPII components. Here, we explore the role of post-translational modifications (PTMs) of the model COPII protein Sec24C in this phenotypic switch during mitosis. In interphase, Sec24C is modified by O-linked β-N-acetylglucosamine (O-GlcNAc), and we show that this glycan is rapidly removed upon mitotic entry, influencing the timing of Sec24C dispersal. Additionally, we identify novel, cell cycle phase-enriched phosphorylation events on Sec24C, including phosphosites that regulate the stability and localization of the protein, providing the first systematic characterization of dynamic PTMs on any Sec24 protein. Together, our data support the hypothesis that phosphorylation and glycosylation of Sec24C act in concert to induce rapid dispersal upon mitotic entry and may promote equal partitioning of the endomembrane system to daughter cells after division.

  PublisherOA PDFDOI

• Evidence for Functional Regulation of the KLHL3/WNK Pathway by O-GlcNAcylation

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-02-27

  preprintOpen accessSenior authorCorresponding

  Abstract The 42-member Kelch-like (KLHL) protein family are adaptors for ubiquitin E3 ligase complexes, governing the stability of a wide range of substrates. KLHL proteins are critical for maintaining proteostasis in a variety of tissues and are mutated in human diseases, including cancer, neurodegeneration, and familial hyperkalemic hypertension. However, the regulation of KLHL proteins remains incompletely understood. Previously, we reported that two KLHL family members, KEAP1 and gigaxonin, are regulated by O-linked β- N -acetylglucosamine (O-GlcNAc), an intracellular form of glycosylation. Interestingly, some ubiquitination targets of KEAP1 and gigaxonin are themselves also O-GlcNAcylated, suggesting that multi-level control by this post-translational modification may influence many KLHL pathways. To test this hypothesis, we examined KLHL3, which ubiquitinates with-no-lysine (WNK) kinases to modulate downstream ion channel activity. Our biochemical and glycoproteomic data demonstrate that human KLHL3 and all four WNK kinases (WNK1-4) are O-GlcNAcylated. Moreover, our results suggest that O-GlcNAcylation affects WNK4 function in both osmolarity control and ferroptosis, with potential implications ranging from blood pressure regulation to neuronal health and survival. This work demonstrates the functional regulation of the KLHL3/WNK axis by O-GlcNAcylation and supports a broader model of O-GlcNAc serving as a general regulator of KLHL signaling and proteostasis.

  PublisherOA PDFDOI

• ASCB statement of commitment to diversity, equity, and inclusion

  Molecular Biology of the Cell · 2024-07-22 · 1 citations

  editorialOpen access

  Published version

  PublisherOA PDFDOI

• Sugar Highs: Recent Notable Breakthroughs in Glycobiology

  Biochemistry · 2024-10-30 · 4 citations

  reviewSenior authorCorresponding

  Glycosylation is biochemically complex and functionally critical to a wide range of processes and disease states, making it a vibrant area of contemporary research. Here, we highlight a selection of notable recent advances in the glycobiology of SARS-CoV-2 infection and immunity, cancer biology and immunotherapy, and newly discovered glycosylated RNAs. Together, these studies illustrate the significance of glycosylation in normal biology and the great promise of manipulating glycosylation for therapeutic benefit in disease.

  PublisherDOI

• The 2022 Nobel Prize in Chemistry—sweet!

  Glycobiology · 2023-03-01 · 7 citations

  articleOpen access1st authorCorresponding

  On 2022 October 5, The Royal Swedish Academy of Sciences announced its decision to award the Nobel Prize in Chemistry 2022 to Carolyn R. Bertozzi (Stanford University), Morten Meldal (University of Copenhagen), and K. Barry Sharpless (Scripps Research) “for the development of click chemistry and bioorthogonal chemistry.” The glycobiology community was exultant! To understand why, one must appreciate how challenges in glycoscience research motivated the development of these transformative chemical tools. Glycoscience has a storied history contributing significant discoveries to hematology, metabolism, microbiology, and other fields of biomedical research throughout much of the 20th century. But when the 1970s and 80s ushered in new molecular biology methods that accelerated studies of nucleic acid and protein function, studies of glycans began to lag behind (National Research Council 2012; Agre et al. 2016). Fortunately, since then, vast improvements have been made in areas such as carbohydrate synthesis and glycan arrays (Rillahan and Paulson 2011; Li and Bennett 2022), availability of glyco-enzymes and small molecule inhibitors (Moremen et al. 2018; Almahayni et al. 2022), mass spectrometry analysis of glycans and glycopeptides (Ruhaak et al. 2018; Suttapitugsakul et al. 2020; Bagdonaite et al. 2022), as well understanding of biological systems (Varki 2017), all of which have facilitated studies of glycan function. Notwithstanding these and other important advances, glycan detection has presented a recurrent challenge. Indeed, much of the modern practice of biological research hinges on the ability to specifically address a biomolecule of interest so that it can be isolated, visualized, or quantified. For nucleic acids, this can often be achieved via hybridization, whereas specific proteins can be detected and tracked using antibodies or protein tagging methods. But genetically encoded tags cannot be used to track glycans, which are not primary gene products. For the glycobiologist, lectins and antibodies have been essential tools but can suffer from limitations relating to specificity and affinity (Cummings et al. 2022).

  PublisherOA PDFDOI

• O-GlcNAcylation regulates neurofilament-light assembly and function and is perturbed by Charcot-Marie-Tooth disease mutations

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-02-22

  preprintOpen accessSenior authorCorresponding

  Abstract The neurofilament (NF) cytoskeleton is critical for neuronal morphology and function. In particular, the neurofilament-light (NF-L) subunit is required for NF assembly in vivo and is mutated in subtypes of Charcot-Marie-Tooth (CMT) disease. NFs are highly dynamic, and the regulation of NF assembly state is incompletely understood. Here, we demonstrate that human NF-L is modified in a nutrient-sensitive manner by O-linked-β- N -acetylglucosamine (O-GlcNAc), a ubiquitous form of intracellular glycosylation. We identify five NF-L O-GlcNAc sites and show that they regulate NF assembly state. Interestingly, NF-L engages in O-GlcNAc-mediated protein-protein interactions with itself and with the NF component α-internexin, implying that O-GlcNAc is a general regulator of NF architecture. We further show that NF-L O-GlcNAcylation is required for normal organelle trafficking in primary neurons, underlining its functional significance. Finally, several CMT-causative NF-L mutants exhibit perturbed O-GlcNAc levels and resist the effects of O-GlcNAcylation on NF assembly state, indicating a potential link between dysregulated O-GlcNAcylation and pathological NF aggregation. Our results demonstrate that site-specific glycosylation regulates NF-L assembly and function, and aberrant NF O-GlcNAcylation may contribute to CMT and other neurodegenerative disorders.

  PublisherOA PDFDOI

Recent grants

• Cell signaling through O-GlcNAc reader proteins

  NIH · $2.8M · 2016–2027

• Metabolic regulation of KLHL proteins through O-glycosylation

  NIH · $1.6M · 2019–2024

• Control of COPII vesicle trafficking by intracellular protein glycosylation

  NIH · $2.6M · 2017–2025

Frequent coauthors

• Junying Yuan

  China Medical University

  44 shared

• Dawei Ma

  29 shared

• Kai Long

  Shanghai CASB Biotechnology (China)

  29 shared

• Kevin F. Bryant

  Active Motif (United States)

  26 shared

• Donald M. Coen

  Boston VA Research Institute

  26 shared

• Donalyn Scheuner

  25 shared

• David Ron

  University of Cambridge

  25 shared

• Heather P. Harding

  University of Cambridge

  25 shared