Work

VASH1 phosphorylation regulates tubulin detyrosination via CNP/PRKG1α signaling in DRG neurons

Year: 2026

Type: preprint

Abstract: 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 1α (CNP/cGMP/PRKG1α) 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 PRKG1α 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 PRKG1α 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. SUMMARY This study identifies VASH1-SVBP as a key downstream effector of the CNP/cGMP/PRKG1α signaling cascade, revealing how an extracellular cue regulates microtubule detyrosination and dynamics to shape growth cone morphology during dorsal root ganglion neuron development.

Source: bioRxiv (Cold Spring Harbor Laboratory)

DOI: 10.64898/2026.10.14.759141