VASH1-SVBP and VASH2-SVBP generate different detyrosination profiles on microtubules

The detyrosination/tyrosination cycle of α-tubulin is critical for proper cell functioning. VASH1-SVBP and VASH2-SVBP are ubiquitous enzymes involved in microtubule detyrosination, whose mode of action is little known. Here, we show in reconstituted systems and cells that VASH1-SVBP and VASH2-SVBP d...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of cell biology 2023-02, Vol.222 (2), p.1
Main Authors: Ramirez-Rios, Sacnicte, Choi, Sung Ryul, Sanyal, Chadni, Blum, Thorsten B, Bosc, Christophe, Krichen, Fatma, Denarier, Eric, Soleilhac, Jean-Marc, Blot, Béatrice, Janke, Carsten, Stoppin-Mellet, Virginie, Magiera, Maria M, Arnal, Isabelle, Steinmetz, Michel O, Moutin, Marie-Jo
Format: Article
Language:English
Subjects:
Angiogenic Proteins - metabolism
Binding
Biochemistry
Carrier Proteins - metabolism
Cell Cycle Proteins - metabolism
Confined spaces
Cryoelectron Microscopy
Cytoskeleton
Electron microscopy
Enzymes
Lattices
Life Sciences
Microtubules
Microtubules - metabolism
Mode of action
Structural Biology
Subpopulations
Tubulin
Tubulin - metabolism
Tyrosine - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The detyrosination/tyrosination cycle of α-tubulin is critical for proper cell functioning. VASH1-SVBP and VASH2-SVBP are ubiquitous enzymes involved in microtubule detyrosination, whose mode of action is little known. Here, we show in reconstituted systems and cells that VASH1-SVBP and VASH2-SVBP drive the global and local detyrosination of microtubules, respectively. We solved the cryo-electron microscopy structure of VASH2-SVBP bound to microtubules, revealing a different microtubule-binding configuration of its central catalytic region compared to VASH1-SVBP. We show that the divergent mode of detyrosination between the two enzymes is correlated with the microtubule-binding properties of their disordered N- and C-terminal regions. Specifically, the N-terminal region is responsible for a significantly longer residence time of VASH2-SVBP on microtubules compared to VASH1-SVBP. We suggest that this VASH region is critical for microtubule detachment and diffusion of VASH-SVBP enzymes on lattices. Our results suggest a mechanism by which VASH1-SVBP and VASH2-SVBP could generate distinct microtubule subpopulations and confined areas of detyrosinated lattices to drive various microtubule-based cellular functions.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.202205096