Mixed-lineage leukemia protein 2 suppresses ciliary assembly by the modulation of actin dynamics and vesicle transport

Cell Discovery

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[1] 0000 0000 9878 7032, grid.216938.7, State 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, 300071, Tianjin, China;0000 0000 9878 7032, grid.216938.7, State 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, 300071, Tianjin, China;grid.410585.d, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Institute of Biomedical Sciences, College of Life Sciences, Shandong Normal University, 250014, Jinan, Shandong, China;grid.410585.d, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Institute of Biomedical Sciences, College of Life Sciences, Shandong Normal University, 250014, Jinan, Shandong, China;

DOI  :  10.1038/s41421-019-0100-3

来源: publisher

【 摘 要 】

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.

【 授权许可】

CC BY