A Sweet Embrace: Control of Protein–Protein Interactions by O-Linked β-<i>N</i>-Acetylglucosamine

Tarbet, Heather J; Toleman, Clifford A.; Boyce, Michael

doi:10.1021/acs.biochem.7b00871

Cited by 34 publications

(26 citation statements)

References 93 publications

(243 reference statements)

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“…Because IF proteins self-associate into homo-oligomeric complexes, we hypothesized that vimentin O-GlcNAcylation might influence its protein-protein interactions. Indeed, O-GlcNAc regulates protein-protein interactions in other contexts, including chromatin remodeling, nutrient sensing, and the interaction between keratins and Akt ( Ku et al, 2010 ; Fujiki et al, 2011 ; Tarbet et al, 2018 ; Dentin et al, 2008 ). However, physiological O-GlcNAc-mediated interactions are often low-affinity, sub-stoichiometric, and transient, presenting a technical barrier to studying them ( Hanover et al, 2010 ; Hart et al, 2011 ; Shafi et al, 2000 ; Keembiyehetty et al, 2015 ; Mondoux et al, 2011 ; Bond and Hanover, 2013 ; Tarbet et al, 2018 ).…”

Section: Resultsmentioning

confidence: 99%

Site-specific glycosylation regulates the form and function of the intermediate filament cytoskeleton

Tarbet

Dolat

Smith

et al. 2018

eLife

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Intermediate filaments (IF) are a major component of the metazoan cytoskeleton and are essential for normal cell morphology, motility, and signal transduction. Dysregulation of IFs causes a wide range of human diseases, including skin disorders, cardiomyopathies, lipodystrophy, and neuropathy. Despite this pathophysiological significance, how cells regulate IF structure, dynamics, and function remains poorly understood. Here, we show that site-specific modification of the prototypical IF protein vimentin with O-linked β-N-acetylglucosamine (O-GlcNAc) mediates its homotypic protein-protein interactions and is required in human cells for IF morphology and cell migration. In addition, we show that the intracellular pathogen Chlamydia trachomatis, which remodels the host IF cytoskeleton during infection, requires specific vimentin glycosylation sites and O-GlcNAc transferase activity to maintain its replicative niche. Our results provide new insight into the biochemical and cell biological functions of vimentin O-GlcNAcylation, and may have broad implications for our understanding of the regulation of IF proteins in general.

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Section: Resultsmentioning

confidence: 99%

Site-specific glycosylation regulates the form and function of the intermediate filament cytoskeleton

Tarbet

Dolat

Smith

et al. 2018

eLife

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“…Although numerous PTMs have been mapped on components of the early secretory pathway, we still have only an elementary understanding of their contributions to membrane trafficking. β‐linked N‐acetylglucosamine (O‐GlcNAc) modifications are found frequently at serine and threonine residues on both nuclear and cytoplasmic proteins . These modifications are highly reversible and cycle on and off rapidly throughout the lifetime of the protein.…”

Section: Regulation Of Copii Carrier Formation and Transport Mediatedmentioning

confidence: 99%

COPII‐mediated trafficking at the ER/ERGIC interface

Peotter

Kasberg

Pustova

et al. 2019

Traffic

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Coat proteins play multiple roles in the life cycle of a membrane-bound transport intermediate, functioning in lipid bilayer remodeling, cargo selection and targeting to an acceptor compartment. The Coat Protein complex II (COPII) coat is known to act in each of these capacities, but recent work highlights the necessity for numerous accessory factors at all stages of transport carrier existence. Here, we review recent findings that highlight the roles of COPII and its regulators in the biogenesis of tubular COPII-coated carriers in mammalian cells that enable cargo transport between the endoplasmic reticulum and ER-Golgi intermediate compartments, the first step in a series of trafficking events that ultimately allows for the distribution of biosynthetic secretory cargoes throughout the entire endomembrane system. K E Y W O R D S COPII coat, early secretory pathway, endoplasmic reticulum, ER exit site, posttranslational modification, Sec16A, Tango1/cTAGE5, TFG

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“…The modification of proteins with O‐GlcNAc is thus limited by UDP‐GlcNAc availability and occurs in a specific manner on serine or threonine residues of nearly 4000 proteins, thus modulating protein‐protein interactions, phosphorylation and enzymatic stability . In this manner, protein modification by O‐GlcNAc controls a wide range of processes including signaling networks, transcription, cell metabolism, amino acid and nucleotide metabolism, nutrient sensing and the cell stress response .…”

Section: Direct Control Of Endocytic Membrane Traffic By Metabolitesmentioning

confidence: 99%

Energetic adaptations: Metabolic control of endocytic membrane traffic

Rahmani

Defferrari

Wakarchuk

et al. 2019

Traffic

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Endocytic membrane traffic controls the access of myriad cell surface proteins to the extracellular milieu, and thus gates nutrient uptake, ion homeostasis, signaling, adhesion and migration. Coordination of the regulation of endocytic membrane traffic with a cell's metabolic needs represents an important facet of maintenance of homeostasis under variable conditions of nutrient availability and metabolic demand. Many studies have revealed intimate regulation of endocytic membrane traffic by metabolic cues, from the specific control of certain receptors or transporters, to broader adaptation or remodeling of the endocytic membrane network. We examine how metabolic sensors such as AMP‐activated protein kinase, mechanistic target of rapamycin complex 1 and hypoxia inducible factor 1 determine sufficiency of various metabolites, and in turn modulate cellular functions that includes control of endocytic membrane traffic. We also examine how certain metabolites can directly control endocytic traffic proteins, such as the regulation of specific protein glycosylation by limiting levels of uridine diphosphate N‐acetylglucosamine (UDP‐GlcNAc) produced by the hexosamine biosynthetic pathway. From these ideas emerge a growing appreciation that endocytic membrane traffic is orchestrated by many intrinsic signals derived from cell metabolism, allowing alignment of the functions of cell surface proteins with cellular metabolic requirements. Endocytic membrane traffic determines how cells interact with their environment, thus defining many aspects of nutrient uptake and energy consumption. We examine how intrinsic signals that reflect metabolic status of a cell regulate endocytic traffic of specific proteins, and, in some cases, exert broad control of endocytic membrane traffic phenomena. Hence, endocytic traffic is versatile and adaptable and can be modulated to meet the changing metabolic requirements of a cell.

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A Sweet Embrace: Control of Protein–Protein Interactions by O-Linked β-N-Acetylglucosamine

Cited by 34 publications

References 93 publications

Site-specific glycosylation regulates the form and function of the intermediate filament cytoskeleton

Site-specific glycosylation regulates the form and function of the intermediate filament cytoskeleton

COPII‐mediated trafficking at the ER/ERGIC interface

Energetic adaptations: Metabolic control of endocytic membrane traffic

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