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Updated: Jan 22, 2026

Using Microfluidics and Fluorescence Microscopy to Study the Assembly Dynamics of Single Actin Filaments and Bundles
Published on: May 5, 2022
Mixed-lineage leukemia protein 2 suppresses ciliary assembly by the modulation of actin dynamics and vesicle
Yang Yang1, Huijie Hao1, Xiaofan Wu1
11State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of the Ministry of Education, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin, 300071 China.
Abstract:
Primary cilia are critically involved in the coordination of diverse signaling pathways and ciliary defects are associated with a variety of human diseases. The past decades have witnessed great progress in the core machinery orchestrating ciliary assembly. However, the upstream epigenetic cues that direct ciliogenesis remain elusive. Herein, we demonstrate that mixed-lineage leukemia protein 2 (MLL2), a histone methyltransferase, plays a negative role in ciliogenesis. RNA-sequencing analysis reveals that the expression of five actin-associated proteins is significantly downregulated in MLL2-depleted cells. Overexpression of these proteins partially rescues ciliary abnormality elicited by MLL2 depletion. Our data also show that actin dynamics is remarkably changed in MLL2-depleted cells, resulting in the impairment of cell adhesion, spreading, and motility. In addition, MLL2 depletion promotes ciliary vesicle trafficking to the basal body in an actin-related manner. Together, these results reveal that MLL2 inhibits ciliogenesis by modulating actin dynamics and vesicle transport, and suggest that alteration of MLL2 may contribute to the pathogenesis of cilium-associated diseases.
Insights
Mixed-lineage leukemia protein 2 (MLL2) inhibits primary cilia assembly by regulating actin dynamics and vesicle transport. MLL2 depletion impairs ciliogenesis, potentially contributing to cilium-associated diseases.
Area of Science:
- Cell Biology
- Epigenetics
- Molecular Biology
Background:
- Primary cilia coordinate signaling pathways; defects cause human diseases.
- Ciliary assembly machinery is well-studied, but upstream epigenetic regulators are unknown.
- Mixed-lineage leukemia protein 2 (MLL2) is a histone methyltransferase.
Purpose of the Study:
- To investigate the role of MLL2 in ciliogenesis.
- To identify epigenetic factors influencing primary cilia assembly.
Main Methods:
- RNA-sequencing to analyze gene expression in MLL2-depleted cells.
- Overexpression studies to assess functional rescue.
- Analysis of actin dynamics, cell adhesion, spreading, and motility.
- Investigation of ciliary vesicle trafficking.
Main Results:
- MLL2 depletion downregulates five actin-associated proteins.
- Overexpression of these proteins partially rescues ciliary defects.
- MLL2 depletion alters actin dynamics, impairing cell adhesion, spreading, and motility.
- MLL2 depletion enhances actin-dependent ciliary vesicle trafficking to the basal body.
Conclusions:
- MLL2 inhibits ciliogenesis by modulating actin dynamics and vesicle transport.
- Altered MLL2 function may contribute to the pathogenesis of cilium-associated diseases.
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