Channelpedia

PubMed 24855944


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Slo1 , TRP , TRPM , TRPM7



Title: The TRPM7 chanzyme is cleaved to release a chromatin-modifying kinase.

Authors: Grigory Krapivinsky, Luba Krapivinsky, Yunona Manasian, David E Clapham

Journal, date & volume: Cell, 2014 May 22 , 157, 1061-72

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24855944


Abstract
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: