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Essential Role of Mg2+ for Mouse Preimplantation Embryo Development Revealed by TRPM7 Chanzyme Deficient Gametes

ABSTRACT: TRPM7 (transient receptor potential cation channel subfamily M member 7) is a chanzyme with channel and kinase domains essential for embryo development. Using gamete-specific Trpm7-null lines, we report that TRPM7-mediated Mg2+ influx is indispensable for reaching the blastocyst stage. TRPM7 was expressed dynamically from gametes to blastocysts, displaying stage-specific and distinct localizations on the plasma membrane, cytoplasm, and nucleus, and undergoes cleavage that produces C- terminal kinase fragments. TRPM7 underpinned Mg2+ homeostasis throughout this time, and excess Mg2+ but not Zn2+ or Ca2+ overcame the arrest of Trpm7-null embryos; expressing Trpm7 mRNA restored development, but mutant versions failed or were less effective. Transcriptomic analyses of embryos lacking Trpm7 revealed an abundance of oxidative stress-pathway genes, confirmed by mitochondrial dysfunction, and a reduction of transcription factor networks essential for proliferation; Mg2+ supplementation corrected these defects. Hence, TRPM7 underpins Mg2+ homeostasis in preimplantation embryos, prevents oxidative stress, and promotes gene expression patterns necessary for developmental progression and cell lineage specification.

ORGANISM(S): Mus musculus

PROVIDER: GSE241487 | GEO | 2024/01/22

REPOSITORIES: GEO

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The molecular appearance of native TRPM7 channel complexes identified by high-resolution proteomics

Project description:The transient receptor potential cation channel, subfamily M, member 7 (TRPM7) is a ubiquitously expressed membrane protein consisting of an ion channel domain and an intracellularly located protein kinase domain. TRPM7 plays a fundamental role in the cellular uptake of divalent cations such as Zn2+, Mg2+ and Ca2+, and thus shapes cellular excitability, plasticity and metabolic activity. The molecular appearance and operation of TRPM7 channel complexes in native tissues have remained unresolved. Here, we investigated the subunit composition of endogenous TRPM7 channels in rodent brain by multi-epitope affinity purification and high-resolution quantitative MS analysis. We found that native TRPM7 channels are high molecular-weight multi-protein complexes that contain the putative metal transporter proteins CNNM1-4 and a small G-protein ARL15. Heterologous reconstitution experiments confirmed the formation of TRPM7/CNNM/ARL15 ternary complexes and indicated that ARL15 effectively and specifically impacts TRPM7 channel activity. These results open up new avenues towards a mechanistic understanding of the cellular regulation and function of TRPM7 channels.

2021-11-29 | PXD025279 | Pride

CNNM proteins selectively bind to the TRPM7 channel to stimulate divalent cation entry into cells

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Expression profiles from HEK293 cells by overexpression of TRPM7 channel

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2011-07-22 | E-GEOD-23102 | biostudies-arrayexpress

Genome-wide comparative analysis of gene expression in wild type (WT3) and TRPM7-/- (K09) mouse embryonic stem cells

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Genome-wide comparative analysis of gene expression in wild type (WT3) and TRPM7-/- (K09) mouse embryonic stem cells

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TRPM7 maintains progenitor-like features of neuroblastoma cells

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Limiting Mrs2-Dependent Mg2+ Uptake Induces Metabolic Programming in Prolonged Dietary Stress

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