Abstract
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.
Highlights
Because Intermediate filaments (IF) proteins self-associate into homo-oligomeric complexes, we hypothesized that vimentin O-GlcNAcylation might influence its protein-protein interactions
We provide evidence that sitespecific glycosylation of the vimentin head domain regulates its homotypic association in human cells, and is required for both IF morphology and cell migration (Figure 6)
Site-specific O-GlcNAcylation of vimentin is exploited by an intracellular pathogen to promote its own replication, underlining the importance of IF dynamics in disease states
Summary
Intermediate filaments (IF) are a major component of the metazoan cytoskeleton, distinct from the actin and microtubule systems (Lowery et al, 2015; Herrmann and Aebi, 2016; Chernyatina et al, 2015; Koster et al, 2015; Leduc and Etienne-Manneville, 2015).
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