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.

Cell Discovery
|July 3, 2019
PubMed

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.
Keywords:
ActinCilia

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