STMND1 Is a Phylogenetically Ancient Stathmin Which Localizes to Motile Cilia and Exhibits Nuclear Translocation That Is Inhibited When Soluble Tubulin Concentration Increases

Authors

Xiang Deng
Bryan O Seguinot
Gary Bradshaw
Jong Suk Lee
Shannon Coy
Marian Kalocsay
Sandro Santagata
Timothy Mitchison

Publication Date

6-1-2024

Journal

Molecular Biology of the Cell

Abstract

Stathmins are small, unstructured proteins that bind tubulin dimers and are implicated in several human diseases, but whose function remains unknown. We characterized a new stathmin, STMND1 (Stathmin Domain Containing 1) as the human representative of an ancient subfamily. STMND1 features a N-terminal myristoylated and palmitoylated motif which directs it to membranes and a tubulin-binding stathmin-like domain (SLD) that contains an internal nuclear localization signal. Biochemistry and proximity labeling showed that STMND1 binds tubulin, and live imaging showed that tubulin binding inhibits translocation from cellular membranes to the nucleus. STMND1 is highly expressed in multiciliated epithelial cells, where it localizes to motile cilia. Overexpression in a model system increased the length of primary cilia. Our study suggests that the most ancient stathmins have cilium-related functions that involve sensing soluble tubulin.

Keywords

Cilia, Tubulin, Humans, Stathmin, Cell Nucleus, Phylogeny, Protein Binding, Nuclear Localization Signals, Animals, Epithelial Cells, Protein Transport, Amino Acid Sequence

Comments

Supplementary Material

PMID: 38630521

DOI

10.1091/mbc.E23-12-0514

PMID

38630521

PMCID

PMC11238091

PubMedCentral® Posted Date

May 2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes