Faculty, Staff and Student Publications
Language
English
Publication Date
12-1-2025
Journal
Journal of Cell Biology
DOI
10.1083/jcb.202502192
PMID
41171096
PMCID
PMC12803766
PubMedCentral® Posted Date
1-15-2026
PubMedCentral® Full Text Version
Author MSS
Abstract
The small, tubulin-binding protein STMN2 is highly expressed in neurons and is implicated in amyotrophic lateral sclerosis. STMN2 degrades rapidly and accumulates at axotomy sites, suggesting fast turnover is crucial for its neuroprotective function. We show that STMN2 was primarily degraded by the ubiquitin-proteasome system. Its membrane-targeting N-terminal domain promoted fast turnover, whereas its tubulin-binding domain promoted stabilization. Proximity labeling and imaging showed that tubulin binding reduced STMN2 targeting to trans-Golgi network membranes. Pull-down assays showed that tubulin binds preferentially to soluble over membrane-bound STMN2. Our observations suggest that STMN2 interconverts between a soluble, tubulin-bound form and a membrane-bound, tubulin-free form, and is rapidly degraded when released from both membranes and tubulin. We propose that tubulin binding sequesters and stabilizes STMN2, while its neuroprotective function involves an unknown membrane activity.
Keywords
Tubulin, Humans, Protein Binding, Animals, Protein Stability, Proteasome Endopeptidase Complex, trans-Golgi Network, Proteolysis, Cell Membrane, HEK293 Cells, Protein Transport, Solubility
Published Open-Access
yes
Recommended Citation
Deng, Xiang; Bradshaw, Gary A; Kalocsay, Marian; et al., "Tubulin Regulates Stability and Localization of STMN2 by Binding Preferentially to Its Soluble Form" (2025). Faculty, Staff and Student Publications. 5948.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5948
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