Glutamylated vimentin proteoform identified by a synthetic binder links to epithelial-mesenchymal plasticity
Ganie, R. A.; Biswas, A.; Sasi, S.; Devarakonda, L. P.; Kale, I.; Mullick, S.; Siddappa, G.; Singh, N.; Gadadhar, S.; Sirajuddin, M.
Show abstract
Cytoskeletal protein expression and filament dynamics change significantly during cell state transitions. However, post-translational modifications of cytoskeletal proteins during these transitions have rarely been described. Here, using a synthetic glutamylation-binder (SB2B49) selected against a bi-glutamylated peptide epitope, we identify a distinct pool of glutamylated vimentin filaments. We demonstrate that vimentin glutamylation is enzymatically added by tubulin tyrosine ligase-like (TTLLs) and removed by cytosolic carboxypeptidases (CCPs). Mass spectrometry and mutagenesis reveal that glutamylation occurs on specific vimentin residues. We find that glutamylated vimentin levels are dynamically modulated during epithelial-mesenchymal plasticity. During collective migration in scratch-wound assays, glutamylated vimentin filaments are transiently depleted at the wound edge, a process controlled by canonical glutamylation writer-erasers. Our findings reveal a new layer of vimentin regulation via glutamylation and establish the glutamylation-binder as a valuable tool for exploring the diversity of vimentin proteoforms and glutamylation modifications in both physiological and pathological contexts.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Rapid and specific degradation of endogenous proteins in mouse models using auxin-inducible degrons 96%
- C-terminal tagging, transmembrane domain hydrophobicity, and an ER retention motif influence the secretory trafficking of the inner nuclear membrane protein emerin 96%
- Secreted exosomes induce filopodia formation 96%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.