Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/106244
Title: The methyltransferase Ezh2 controls cell adhesion and migration through direct methylation of the extranuclear regulatory protein talin
Authors: Ginhoux, Florent
Su, I-hsin
Gunawan, Merry
Venkatesan, Nandini
Loh, Jia Tong
Wong, Jong Fu
Berger, Heidi
Neo, Wen Hao
Li, Liang Yao Jackson
La Win, Myint Khun
Yau, Yin Hoe
Guo, Tiannan
See, Peter Chi Ee
Yamazaki, Sayuri
Chin, Keh Chuang
Gingras, Alexandre R.
Shochat, Susana Geifman
Ng, Lai Guan
Sze, Siu Kwan
Keywords: DRNTU::Science::Biological sciences::Microbiology::Immunology
Issue Date: 2015
Source: Gunawan, M., Venkatesan, N., Loh, J. T., Wong, J. F., Berger, H., Neo, W. H., et al. (2015). The methyltransferase Ezh2 controls cell adhesion and migration through direct methylation of the extranuclear regulatory protein talin. Nature Immunology, 16(5), 505-516.
Series/Report no.: Nature immunology
Abstract: A cytosolic role for the histone methyltransferase Ezh2 in regulating lymphocyte activation has been suggested, but the molecular mechanisms underpinning this extranuclear function have remained unclear. Here we found that Ezh2 regulated the integrin signaling and adhesion dynamics of neutrophils and dendritic cells (DCs). Ezh2 deficiency impaired the integrin-dependent transendothelial migration of innate leukocytes and restricted disease progression in an animal model of multiple sclerosis. Direct methylation of talin, a key regulatory molecule in cell migration, by Ezh2 disrupted the binding of talin to F-actin and thereby promoted the turnover of adhesion structures. This regulatory effect was abolished by targeted disruption of the interactions of Ezh2 with the cytoskeletal-reorganization effector Vav1. Our studies reveal an unforeseen extranuclear function for Ezh2 in regulating adhesion dynamics, with implications for leukocyte migration, immune responses and potentially pathogenic processes.
URI: https://hdl.handle.net/10356/106244
http://hdl.handle.net/10220/34629
DOI: 10.1038/ni.3125
Rights: © 2015 Nature America, Inc. This is the author created version of a work that has been peer reviewed and accepted for publication by Nature Immunology, Nature America, Inc. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1038/ni.3125].
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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