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The TRPM7 Chanzyme Is Cleaved to Release a Chromatin-Modifying Kinase
Open accessAbstract
SUMMARY TRPM7 is a ubiquitous ion channel and kinase, a unique ‘chanzyme’, required for proper early embryonic development. It conducts Zn2+, Mg2+, Ca2+ as well as monovalent cations, and contains a functional serine/threonine kinase at its carboxyl terminus. Here, we show that in normal tissues and cell lines, the kinase is proteolytically cleaved from the channel domain in a cell type-specific manner. These TRPM7 Cleaved Kinase fragments (M7CKs) translocate to the nucleus and bind multiple components of chromatin remodeling complexes, including Polycomb group proteins. In the nucleus, the kinase phosphorylates specific serines/threonines of histones. M7CK-dependent phosphorylation of H3Ser10 at promoters of TRPM7-dependent genes correlates with their activity. We also demonstrate that cytosolic free [Zn2+] is TRPM7-dependent and regulates M7CK binding to transcription factors containing zinc-finger domains. These findings suggest that TRPM7-mediated modulation of intracellular Zn2+ concentration couples ion channel signaling to epigenetic chromatin covalent modifications that affect gene expression patterns.
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Cites
Conversion of embryonic stem cells into neuroectodermal precursors in adherent monoculture
Ying, Q.-L., Stavridis, M., Griffiths, D., Li, M., & Smith, A. (2003) · Nature Biotechnology · doi:10.1038/nbt780 · Cited by 1,504
Signaling to Chromatin through Histone Modifications
Cheung, P., Allis, C. D., & Sassone-Corsi, P. (2000) · Cell · doi:10.1016/s0092-8674(00)00118-5 · Cited by 989
PKM2 Phosphorylates Histone H3 and Promotes Gene Transcription and Tumorigenesis
Yang, W., Xia, Y., Hawke, D., Li, X., Liang, J., Xing, D., Aldape, K., Hunter, T., Alfred Yung, W. K., & Lu, Z. (2012) · Cell · doi:10.1016/j.cell.2012.07.018 · Cited by 846
Assembly and function of DNA double-strand break repair foci in mammalian cells
Bekker-Jensen, S., & Mailand, N. (2010) · DNA Repair · doi:10.1016/j.dnarep.2010.09.010 · Cited by 338
Emerging roles for chromatin as a signal integration and storage platform
Badeaux, A. I., & Shi, Y. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3545 · Cited by 291
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Coupling enzymatic activity and gating in an ancient TRPM chanzyme and its molecular evolution
Huang, Y., Kumar, S., Lee, J., Lü, W., & Du, J. (2024) · Nature Structural & Molecular Biology · doi:10.1038/s41594-024-01316-4 · Cited by 16
Structural insights into regulation of CNNM-TRPM7 divalent cation uptake by the small GTPase ARL15
Mahbub, L., Kozlov, G., Zong, P., Lee, E. L., Tetteh, S., Nethramangalath, T., Knorn, C., Jiang, J., Shahsavan, A., Yue, L., et al. (2023) · eLife · doi:10.7554/elife.86129 · Cited by 14
Metadata
- Authors
- Krapivinsky, G., Krapivinsky, L., Manasian, Y., & Clapham, D. E.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 157
- Issue
- 5
- Pages
- 1061-1072
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2078712719
- Cited by
- 183
- References
- 5
- FWCI
- 8.39
- Type
- journal article
- Language
- en
- Open access
- bronze
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