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PreprintCC BY-NC-NDbioRxiv

Conserved tyrosine Y16 acts as a phosphorylation switch controlling Ena/VASP recruitment to sites of actin assembly

  • Jonas Scholz1
  • Julian Kaltenhäuser2,3
  • Jerushah Emerald4
  • Pavel Kats1
  • Thomas Kaufmann1
  • Anat Nitzan4
  • Ute Curth1
  • Klemens Rottner2,3,5
  • Ronen Zaidel-Bar4
  • Jan Faix1
5 affiliations
  1. 1Institute for Biophysical Chemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany
  2. 2Molecular Cell Biology Group, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany
  3. 3Division of Molecular Cell Biology, Institute for Cell and Neurobiology, Technische Universität Braunschweig, Spielmannstraße 7, 38106 Braunschweig, Germany
  4. 4Gray School of Medical Sciences, Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel
  5. 5Braunschweig Integrated Centre of Systems Biology (BRICS), Rebenring 56, 38106 Braunschweig, Germany
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Abstract

Ena/VASP proteins are powerful actin polymerases that accumulate at sites of active actin assembly, including lamellipodial and microspike tips, focal adhesions and pathogen surfaces, where they drive processive filament elongation. However, the mechanisms controlling their recruitment remain elusive. Here, we used cells lacking all Ena/VASP-family members to systematically test phosphomimetic and nonphosphorylatable substitutions at conserved tyrosine and serine residues implicated in subcellular targeting. Combining cell-based reconstitution with biochemical assays, we identify phosphorylation of Y16 in vertebrate Ena/VASP proteins as the decisive inhibitory modification controlling subcellular Ena/VASP recruitment, in contrast to previously proposed roles for Y39 and S157. Corresponding phosphomimetic substitutions in the C. elegans orthologue UNC-34 phenocopied uncoordinated locomotion of UNC-34 null worms, supporting the evolutionary conservation of this regulatory mechanism. Thus, our findings identify a conserved phosphorylation-sensitive switch at the EVH1-FP4 ligand interface that links EVH1-dependent targeting to dynamic control of actin assembly in adhesion, migration and pathogenesis.

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Cite

BibTeXRIS
BibTeX
@misc{scholz2026conserved,
  title = {{Conserved tyrosine Y16 acts as a phosphorylation switch controlling Ena/VASP recruitment to sites of actin assembly}},
  author = {Jonas Scholz and Julian Kaltenhäuser and Jerushah Emerald and Pavel Kats and Thomas Kaufmann and Anat Nitzan and Ute Curth and Klemens Rottner and Ronen Zaidel-Bar and Jan Faix},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.26.761804},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.26.761804v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - Conserved tyrosine Y16 acts as a phosphorylation switch controlling Ena/VASP recruitment to sites of actin assembly
AU  - Jonas Scholz
AU  - Julian Kaltenhäuser
AU  - Jerushah Emerald
AU  - Pavel Kats
AU  - Thomas Kaufmann
AU  - Anat Nitzan
AU  - Ute Curth
AU  - Klemens Rottner
AU  - Ronen Zaidel-Bar
AU  - Jan Faix
PY  - 2026
DA  - 2026/10/26
PB  - bioRxiv
DO  - 10.64898/2026.10.26.761804
UR  - https://www.biorxiv.org/content/10.64898/2026.10.26.761804v1
AB  - Ena/VASP proteins are powerful actin polymerases that accumulate at sites of active actin assembly, including lamellipodial and microspike tips, focal adhesions and pathogen surfaces, where they drive processive filament elongation. However, the mechanisms controlling their recruitment remain elusive. Here, we used cells lacking all Ena/VASP-family members to systematically test phosphomimetic and nonphosphorylatable substitutions at conserved tyrosine and serine residues implicated in subcellular targeting. Combining cell-based reconstitution with biochemical assays, we identify phosphorylation of Y16 in vertebrate Ena/VASP proteins as the decisive inhibitory modification controlling subcellular Ena/VASP recruitment, in contrast to previously proposed roles for Y39 and S157. Corresponding phosphomimetic substitutions in the C. elegans orthologue UNC-34 phenocopied uncoordinated locomotion of UNC-34 null worms, supporting the evolutionary conservation of this regulatory mechanism. Thus, our findings identify a conserved phosphorylation-sensitive switch at the EVH1-FP4 ligand interface that links EVH1-dependent targeting to dynamic control of actin assembly in adhesion, migration and pathogenesis.
SN  - 2692-8205
ER  -