Michael Boyce

Overview:

The Boyce Lab studies mammalian cell signaling through protein glycosylation. For the latest news, project information and publications from our group, please visit our web site at http://www.boycelab.org or follow us on Twitter at https://twitter.com/BoyceLab.

Positions:

Associate Professor of Biochemistry

Biochemistry
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2005

Harvard Medical School

Grants:

Control of COPII vesicle trafficking by intracellular protein glycosylation

Administered By
Biochemistry
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Protein glycosylation in cancer cell signaling and metabolism

Administered By
Biochemistry
Role
Principal Investigator
Start Date
End Date

Control of COPII vesicle trafficking by intracellular protein glycosylation

Administered By
Biochemistry
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

The human UDP-galactose 4'-epimerase (GALE) is required for cell-surface glycome structure and function.

Glycan biosynthesis relies on nucleotidesugars (NS), abundant metabolites that serve as monosaccharide donors for glycosyltransferases. In vivo, signal-dependent fluctuations in NS levels are required to maintain normal cell physiology and are dysregulated in disease, but how mammalian cells regulate NS levels and pathway flux remains largely uncharacterized. To address this knowledge gap, we examined uridine diphosphate (UDP)-galactose 4'-epimerase (GALE), which interconverts two pairs of essential NSs. GALE deletion in human cells triggered major imbalances in its substrate NSs and consequent dramatic changes in glycolipids and glycoproteins, including a subset of integrins and the death receptor Fas. NS dysregulation also directly impacted cell signaling, as GALE-/- cells exhibit Fas hypoglycosylation and hypersensitivity to Fas ligand-induced apoptosis. Our results reveal a new role for GALE-mediated NS regulation in supporting death receptor signaling and may have implications for the molecular etiology of illnesses characterized by NS imbalances, including galactosemia and metabolic syndrome.
Authors
Broussard, A; Florwick, A; Desbiens, C; Nischan, N; Robertson, C; Guan, Z; Kohler, JJ; Wells, L; Boyce, M
MLA Citation
Broussard, Alex, et al. “The human UDP-galactose 4'-epimerase (GALE) is required for cell-surface glycome structure and function..” J Biol Chem, Dec. 2019. Pubmed, doi:10.1074/jbc.RA119.009271.
URI
https://scholars.duke.edu/individual/pub1423433
PMID
31819007
Source
pubmed
Published In
The Journal of Biological Chemistry
Published Date
DOI
10.1074/jbc.RA119.009271

Glycosylation of gigaxonin regulates intermediate filaments: Novel molecular insights into giant axonal neuropathy: supplemental information

Gigaxonin (also known as KLHL16) is an E3 ligase adaptor protein that promotes the ubiquitination and degradation of intermediate filament (IF) proteins. Mutations in human gigaxonin cause the fatal neurodegenerative disease giant axonal neuropathy (GAN), in which IF proteins accumulate and aggregate in axons throughout the nervous system, impairing neuronal function and viability. Despite this pathophysiological significance, the upstream regulation and downstream effects of normal and aberrant gigaxonin function remain incompletely understood. Here, we report that gigaxonin is modified by O-linked-beta-N-acetylglucosamine (O-GlcNAc), a prevalent form of intracellular glycosylation, in a nutrient- and growth factor-dependent manner. Mass spectrometry analyses of human gigaxonin revealed nine candidate sites of O-GlcNAcylation, two of which - serine 272 and threonine 277 - are required for its ability to mediate IF turnover in novel gigaxonin-deficient human cell models that we created. Taken together, these results suggest that nutrient-responsive gigaxonin O-GlcNAcylation forms a regulatory link between metabolism and IF proteostasis. Our work may have significant implications for understanding the non-genetic modifiers of GAN phenotypes and for the optimization of gene therapy for this disease.
Authors
CHEN, PO-HAN; Smith, T; Hu, J; Pan, S; Smith, A; Lu, A; Chi, J-T; Boyce, M
URI
https://scholars.duke.edu/individual/pub1425510
Source
epmc
Published Date
DOI
10.1101/530303

Directing Traffic: Regulation of COPI Transport by Post-translational Modifications

© Copyright © 2019 Luo and Boyce. The coat protein complex I (COPI) is an essential, highly conserved pathway that traffics proteins and lipids between the endoplasmic reticulum (ER) and the Golgi. Many aspects of the COPI machinery are well understood at the structural, biochemical and genetic levels. However, we know much less about how cells dynamically modulate COPI trafficking in response to changing signals, metabolic state, stress or other stimuli. Recently, post-translational modifications (PTMs) have emerged as one common theme in the regulation of the COPI pathway. Here, we review a range of modifications and mechanisms that govern COPI activity in interphase cells and suggest potential future directions to address as-yet unanswered questions.
Authors
Luo, PM; Boyce, M
MLA Citation
Luo, P. M., and M. Boyce. “Directing Traffic: Regulation of COPI Transport by Post-translational Modifications.” Frontiers in Cell and Developmental Biology, vol. 7, Sept. 2019. Scopus, doi:10.3389/fcell.2019.00190.
URI
https://scholars.duke.edu/individual/pub1415390
Source
scopus
Published In
Frontiers in Cell and Developmental Biology
Volume
7
Published Date
DOI
10.3389/fcell.2019.00190

Dynamic Glycosylation Governs the Vertebrate COPII Protein Trafficking Pathway.

The COPII coat complex, which mediates secretory cargo trafficking from the endoplasmic reticulum, is a key control point for subcellular protein targeting. Because misdirected proteins cannot function, protein sorting by COPII is critical for establishing and maintaining normal cell and tissue homeostasis. Indeed, mutations in COPII genes cause a range of human pathologies, including cranio-lenticulo-sutural dysplasia (CLSD), which is characterized by collagen trafficking defects, craniofacial abnormalities, and skeletal dysmorphology. Detailed knowledge of the COPII pathway is required to understand its role in normal cell physiology and to devise new treatments for disorders in which it is disrupted. However, little is known about how vertebrates dynamically regulate COPII activity in response to developmental, metabolic, or pathological cues. Several COPII proteins are modified by O-linked β-N-acetylglucosamine (O-GlcNAc), a dynamic form of intracellular protein glycosylation, but the biochemical and functional effects of these modifications remain unclear. Here, we use a combination of chemical, biochemical, cellular, and genetic approaches to demonstrate that site-specific O-GlcNAcylation of COPII proteins mediates their protein-protein interactions and modulates cargo secretion. In particular, we show that individual O-GlcNAcylation sites of SEC23A, an essential COPII component, are required for its function in human cells and vertebrate development, because mutation of these sites impairs SEC23A-dependent in vivo collagen trafficking and skeletogenesis in a zebrafish model of CLSD. Our results indicate that O-GlcNAc is a conserved and critical regulatory modification in the vertebrate COPII-dependent trafficking pathway.
Authors
Cox, NJ; Unlu, G; Bisnett, BJ; Meister, TR; Condon, BM; Luo, PM; Smith, TJ; Hanna, M; Chhetri, A; Soderblom, EJ; Audhya, A; Knapik, EW; Boyce, M
MLA Citation
Cox, Nathan J., et al. “Dynamic Glycosylation Governs the Vertebrate COPII Protein Trafficking Pathway..” Biochemistry, vol. 57, no. 1, Jan. 2018, pp. 91–107. Pubmed, doi:10.1021/acs.biochem.7b00870.
URI
https://scholars.duke.edu/individual/pub1296262
PMID
29161034
Source
pubmed
Published In
Biochemistry
Volume
57
Published Date
Start Page
91
End Page
107
DOI
10.1021/acs.biochem.7b00870

A critical role of eEF-2K in mediating autophagy in response to multiple cellular stresses.

The phosphorylation of the subunit alpha of eukaryotic translation initiation factor 2 (eIF2alpha), a critical regulatory event in controlling protein translation, has recently been found to mediate the induction of autophagy. However, the mediators of autophagy downstream of eIF2alpha remain unknown. Here, we provide evidence that eIF2alpha phosphorylation is required for phosphorylation of eukaryotic elongation factor 2 (eEF-2) during nutrient starvation. In addition, we show that eukaryotic elongation factor 2 kinase (eEF-2K) is also required for autophagy signaling during ER stress, suggesting that phosphorylation of eEF-2 may serve as an integrator of various cell stresses for autophagy signaling. On the other hand, although the activation of eEF-2K in response to starvation requires the phosphorylation of eIF2alpha, additional pathways relying partly on Ca(2+) flux may control eEF-2K activity during ER stress, as eIF2alpha phosphorylation is dispensable for both eEF-2 phosphorylation and autophagy in this context.
Authors
Py, BF; Boyce, M; Yuan, J
MLA Citation
Py, Bénédicte F., et al. “A critical role of eEF-2K in mediating autophagy in response to multiple cellular stresses..” Autophagy, vol. 5, no. 3, Apr. 2009, pp. 393–96. Pubmed, doi:10.4161/auto.5.3.7762.
URI
https://scholars.duke.edu/individual/pub808780
PMID
19221463
Source
pubmed
Published In
Autophagy
Volume
5
Published Date
Start Page
393
End Page
396
DOI
10.4161/auto.5.3.7762