Spastin Promotes the Migration and Invasion Capability of T98G Glioblastoma Cells by Interacting with Pin1 through Its Microtubule-Binding Domain

Benan Temizci, Seren Kucukvardar, Arzu Karabay*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Microtubule-severing protein Spastin has been shown to co-localize with actin in migratory glioblastoma cells and is linked to glioblastomas’ migration and invasion capacity. However, the effectiveness of Spastin in glioblastoma migration and the molecular mechanism underpinning the orientation of Spastin towards actin filaments remain unknown. Here, we demonstrated that Spastin plays an active role in glioblastoma migration by showing a reduced migratory potential of T98G glioblastoma cells using real-time cell analysis (RTCA) in Spastin-depleted cells. Pull-down assays revealed that a cis–trans isomerase Pin1 interacts with Spastin through binding to the phosphorylated Pin1 recognition motifs in the microtubule-binding domain (MBD), and immunocytochemistry analysis showed that interaction with Pin1 directs Spastin to actin filaments in extended cell regions. Consequently, by utilizing RTCA, we proved that the migration and invasion capacity of T98G glioblastoma cells significantly increased with the overexpression of Spastin, of which the Pin1 recognition motifs in MBD are constitutively phosphorylated, while the overexpression of phospho-mutant form did not have a significant effect on migration and invasion of T98G glioblastoma cells. These findings demonstrate that Pin1 is a novel interaction partner of Spastin, and their interaction drives Spastin to actin filaments, allowing Spastin to contribute to the glioblastomas’ migration and invasion abilities.

Original languageEnglish
Article number427
JournalCells
Volume12
Issue number3
DOIs
Publication statusPublished - Feb 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

Funding

This work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) 217S466 to Arzu Karabay (AK), TUBITAK 121Z608 to Benan Temizci (BT), and Istanbul Technical University TDK-2017-40941 to AK and BT.

FundersFunder number
Türkiye Bilimsel ve Teknolojik Araştırma Kurumu121Z608, 217S466
Istanbul Teknik ÜniversitesiTDK-2017-40941

    Keywords

    • glioblastoma
    • invasion
    • migration
    • phosphorylation
    • Pin1
    • Spastin

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