| First Author | Krapivinsky G | Year | 2014 |
| Journal | Cell | Volume | 157 |
| Issue | 5 | Pages | 1061-72 |
| PubMed ID | 24855944 | Mgi Jnum | J:222132 |
| Mgi Id | MGI:5644004 | Doi | 10.1016/j.cell.2014.03.046 |
| Citation | Krapivinsky G, et al. (2014) The TRPM7 chanzyme is cleaved to release a chromatin-modifying kinase. Cell 157(5):1061-72 |
| abstractText | TRPM7 is a ubiquitous ion channel and kinase, a unique "chanzyme," required for proper early embryonic development. It conducts Zn(2+), Mg(2+), and Ca(2+) 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 [Zn(2+)] is TRPM7 dependent and regulates M7CK binding to transcription factors containing zinc-finger domains. These findings suggest that TRPM7-mediated modulation of intracellular Zn(2+) concentration couples ion-channel signaling to epigenetic chromatin covalent modifications that affect gene expression patterns. PAPERCLIP: |
