Modulating microtubule stability via α-tubulin acetylation partially restores Golgi fragmentation in spinal muscular atrophy

Authors

• PELİN ZOBAROĞLU ÖZERFollow
• MEMET GÖZÜBÖYÜKFollow
• ÖZGE ÇETİNFollow
• NIKO HENSELFollow
• GÜZİN EMECENFollow
• ADAM MALIKFollow
• MELISSA BOWERMANFollow
• PETER CLAUSFollow
• HAYAT ERDEM YURTERFollow
• GAMZE BORA AKOĞLUFollow

Abstract

Background/aim: Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by the loss of survival of motor neuron (SMN) protein. SMN deficiency leads to perturbations of the cytoskeleton, including microtubules, which are mainly involved in motilityrelated cellular processes. However, the molecular mechanisms of microtubule dysregulation in SMA remain elusive. Alpha (α)-tubulin is a structural component of microtubules, and its posttranslational modifications affect microtubule dynamics. Here, we aimed to investigate α-tubulin acetylation and related molecular mechanisms in SMA. Materials and methods: Two different SMA mouse models, the Drosophila melanogaster model and patient-derived fibroblasts, were used in the study. Western blot and quantitative microscopic analysis were performed to analyze α-tubulin acetylation and related mechanisms. Results: The acetylation level of α-tubulin was decreased in the Drosophila model and in SMA patient fibroblast cells but not in mouse models. This decrease in acetylation is associated with upregulation of the major tubulin deacetylase, HDAC6, in patient cells compared with healthy controls. Microtubules play a role in the organization of the Golgi apparatus, and we demonstrated that increasing α-tubulin acetylation by pharmacological inhibition of HDAC6 partially restored the fragmented morphology of the Golgi apparatus in SMA. Conclusion: Our findings provide new insight into the molecular basis of SMA, indicating that cellular pathologies, including abnormal Golgi morphology, are associated with microtubule dysregulations caused by altered α-tubulin posttranslational modifications and regulatory proteins. Our findings support that microtubule perturbations are part of SMA pathology.

Author ORCID Identifier

PELİN ZOBAROĞLU ÖZER: 0000-0003-1607-9481

MEMET GÖZÜBÖYÜK: 0000-0002-4321-6405

ÖZGE ÇETİN: 0000-0001-7701-8397

NIKO HENSEL: 0000-0002-1611-8906

GÜZİN EMECEN: 0000-0001-9223-7205

ADAM MALIK: 0009-0008-2528-1116

MELISSA BOWERMAN: 0000-0002-3579-6403

PETER CLAUS: 0000-0003-3824-9445

HAYAT ERDEM YURTER: 0000-0002-5883-0643

GAMZE BORA AKOĞLU: 0000-0002-4206-8332

DOI

10.55730/1300-0152.2798

Keywords

Spinal muscular atrophy, α-tubulin acetylation, HDAC6, Golgi fragmentation

First Page

158

Last Page

169

Publisher

The Scientific and Technological Research Council of Türkiye (TÜBİTAK)

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

ZOBAROĞLU ÖZER, P, GÖZÜBÖYÜK, M, ÇETİN, Ö, HENSEL, N, EMECEN, G, MALIK, A, BOWERMAN, M, CLAUS, P, ERDEM YURTER, H, & BORA AKOĞLU, G (2026). Modulating microtubule stability via α-tubulin acetylation partially restores Golgi fragmentation in spinal muscular atrophy. Turkish Journal of Biology 50 (2): 158-169. https://doi.org/10.55730/1300-0152.2798