AI Article Synopsis

  • The study identifies the endoplasmic reticulum (ER) as a significant storage site for intracellular magnesium (Mg) and highlights the protein TMEM94 (ERMA) as a key player in its transport.* -
  • TMEM94 is characterized as a multi-pass transmembrane protein with structural similarities to P-type ATPases, featuring unique domains for nucleotide and phosphorylation interactions.* -
  • Research indicates that a specific tyrosine residue in TMEM94 is vital for Mg binding and function, with implications for cardiac health shown in both mice and human heart cells.*

Article Abstract

Intracellular Mg (Mg) is bound with phosphometabolites, nucleic acids, and proteins in eukaryotes. Little is known about the intracellular compartmentalization and molecular details of Mg transport into/from cellular organelles such as the endoplasmic reticulum (ER). We found that the ER is a major Mg compartment refilled by a largely uncharacterized ER-localized protein, TMEM94. Conventional and AlphaFold2 predictions suggest that ERMA (TMEM94) is a multi-pass transmembrane protein with large cytosolic headpiece actuator, nucleotide, and phosphorylation domains, analogous to P-type ATPases. However, ERMA uniquely combines a P-type ATPase domain and a GMN motif for Mg uptake. Experiments reveal that a tyrosine residue is crucial for Mg binding and activity in a mechanism conserved in both prokaryotic (mgtB and mgtA) and eukaryotic Mg ATPases. Cardiac dysfunction by haploinsufficiency, abnormal Ca cycling in mouse Erma cardiomyocytes, and ERMA mRNA silencing in human iPSC-cardiomyocytes collectively define ERMA as an essential component of Mg uptake in eukaryotes.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10997467PMC
http://dx.doi.org/10.1016/j.molcel.2024.02.033DOI Listing

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Article Synopsis
  • The study identifies the endoplasmic reticulum (ER) as a significant storage site for intracellular magnesium (Mg) and highlights the protein TMEM94 (ERMA) as a key player in its transport.* -
  • TMEM94 is characterized as a multi-pass transmembrane protein with structural similarities to P-type ATPases, featuring unique domains for nucleotide and phosphorylation interactions.* -
  • Research indicates that a specific tyrosine residue in TMEM94 is vital for Mg binding and function, with implications for cardiac health shown in both mice and human heart cells.*
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