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Updated: Jun 15, 2026
Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
Published on: August 7, 2018
Mitosis Localization Signal (MLS) extends KA1 and regulates MELK kinase localization to plasma membrane and activity
Caroline Badouel1, Guillaume Hatte1, Claude Prigent2
1Université de Rennes, CNRS, IGDR (Institut de Génétique et Développement de Rennes) - UMR 6290, F-35000, Rennes, France.
Abstract:
MELK is a cell-cycle dependent serine/threonine protein kinase whose expression is elevated in proliferating and cancer cells. In the Xenopus embryo, MELK overexpression induces cytokinesis failure, leading to multinucleated cells. This phenotype requires MELK catalytic activity, which correlates with MELK conformational modification and its localization to the cell membrane. How MELK activation and localization are coordinated remains unclear. Here, we show that in Xenopus gastrula epithelial cells MELK is abruptly enriched at the plasma membrane starting precisely from the metaphase-to-anaphase transition until early interphase. We show that deletion of the Kinase-Associated domain 1 (KA1), involved in binding to anionic phospholipids, does not abolish MELK localization to the plasma membrane. By a series of deletions, we identified a new 41-amino-acid domain, called Mitosis Localization Signal (MLS) that regulates MELK localization to the plasma membrane in dividing cells. We show that MLS cooperates with KA1 to regulate MELK localization and is necessary to induce cytokinesis failure when MELK is overexpressed. Our findings highlight the importance of MLS in MELK localization and in regulating MELK activity.
Insights
The study identified a new domain, the Mitosis Localization Signal (MLS), crucial for MELK protein localization to the plasma membrane during cell division. This MLS domain, along with KA1, is essential for MELK
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Melting kinase (MELK) is a serine/threonine kinase upregulated in cancer.
- MELK overexpression in Xenopus embryos causes cytokinesis failure, resulting in multinucleated cells.
- MELK's catalytic activity, conformational changes, and cell membrane localization are linked to its function, but the coordination of activation and localization is unknown.
Purpose of the Study:
- To investigate the mechanisms coordinating MELK activation and plasma membrane localization during cell division.
- To identify specific domains within MELK responsible for its localization to the plasma membrane.
Main Methods:
- Utilized Xenopus gastrula epithelial cells for live imaging and analysis of MELK localization.
- Employed deletion mutagenesis to identify functional domains within MELK.
- Investigated the role of the Kinase-Associated domain 1 (KA1) and a newly identified domain (MLS) in MELK localization.
Main Results:
- MELK is enriched at the plasma membrane from metaphase to early interphase in Xenopus gastrula epithelial cells.
- Deletion of the KA1 domain does not prevent MELK plasma membrane localization.
- A novel 41-amino acid domain, the Mitosis Localization Signal (MLS), was identified as critical for MELK plasma membrane localization in dividing cells.
- MLS cooperates with KA1 to regulate MELK localization and is essential for MELK-induced cytokinesis failure.
Conclusions:
- The Mitosis Localization Signal (MLS) is a key regulator of MELK localization to the plasma membrane during mitosis.
- MLS and KA1 work together to control MELK localization and activity.
- Understanding MELK localization is crucial for comprehending its role in cell division and cancer progression.
