VASH1 phosphorylation regulates tubulin detyrosination via CNP/PRKG1α signaling in DRG neurons.
- 1University Grenoble Alpes, Inserm, U1216, CNRS, CEA, Grenoble Institute of Neurosciences, Grenoble, France.
Abstract
Functional neuronal circuit formation requires precise regulation of axon growth and branching through dynamic cytoskeletal remodeling. Although microtubule detyrosination/re-tyrosination critically controls microtubule dynamics, how extracellular signals regulate this process remains unclear. Here, we identify a direct link between C-type natriuretic peptide, protein kinase cGMP-dependent 1 (CNP/cGMP/PRKG1) signaling and microtubule detyrosination in dorsal root ganglion (DRG) neurons. CNP stimulation induces growth cone enlargement, increases tyrosinated tubulin within growth cones, and reduces detyrosinated tubulin along axons, effects abolished by PRKG1 inhibition. Pharmacological inhibition or genetic deletion of the detyrosinating enzyme VASH1 phenocopies CNP-induced growth cone remodeling. In vitro kinase assays identify VASH1 as a direct PRKG1 substrate and reveal a specific C-terminal serine phosphorylation site (serine 337) that suppresses VASH1-SVBP microtubule association and detyrosination activity. Together, these findings establish VASH1-SVBP as a key downstream effector linking extracellular guidance signaling to microtubule remodeling during DRG neuronal development.
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BibTeX
@misc{sanyal2026vash1,
title = {{VASH1 phosphorylation regulates tubulin detyrosination via CNP/PRKG1α signaling in DRG neurons.}},
author = {C. Sanyal and S. Ismail and C. Bosc and E. Denarier and J.-M. Soleilhac and B. Blot and V. Pakulska and A. Kraut and Y. Coute and A. Andrieux and L. Carrier and S. Ramirez-Rios and M.-J. Moutin},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.14.759141},
url = {https://www.biorxiv.org/content/10.64898/2026.10.14.759141v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - VASH1 phosphorylation regulates tubulin detyrosination via CNP/PRKG1α signaling in DRG neurons.
AU - C. Sanyal
AU - S. Ismail
AU - C. Bosc
AU - E. Denarier
AU - J.-M. Soleilhac
AU - B. Blot
AU - V. Pakulska
AU - A. Kraut
AU - Y. Coute
AU - A. Andrieux
AU - L. Carrier
AU - S. Ramirez-Rios
AU - M.-J. Moutin
PY - 2026
DA - 2026/10/14
PB - bioRxiv
DO - 10.64898/2026.10.14.759141
UR - https://www.biorxiv.org/content/10.64898/2026.10.14.759141v1
AB - Functional neuronal circuit formation requires precise regulation of axon growth and branching through dynamic cytoskeletal remodeling. Although microtubule detyrosination/re-tyrosination critically controls microtubule dynamics, how extracellular signals regulate this process remains unclear. Here, we identify a direct link between C-type natriuretic peptide, protein kinase cGMP-dependent 1 (CNP/cGMP/PRKG1) signaling and microtubule detyrosination in dorsal root ganglion (DRG) neurons. CNP stimulation induces growth cone enlargement, increases tyrosinated tubulin within growth cones, and reduces detyrosinated tubulin along axons, effects abolished by PRKG1 inhibition. Pharmacological inhibition or genetic deletion of the detyrosinating enzyme VASH1 phenocopies CNP-induced growth cone remodeling. In vitro kinase assays identify VASH1 as a direct PRKG1 substrate and reveal a specific C-terminal serine phosphorylation site (serine 337) that suppresses VASH1-SVBP microtubule association and detyrosination activity. Together, these findings establish VASH1-SVBP as a key downstream effector linking extracellular guidance signaling to microtubule remodeling during DRG neuronal development.
ER -