ERMA (TMEM94) is a P-type ATPase transporter for Mg2+ uptake in the endoplasmic reticulum.
Mol Cell
; 84(7): 1321-1337.e11, 2024 Apr 04.
Article
in En
| MEDLINE
| ID: mdl-38513662
ABSTRACT
Intracellular Mg2+ (iMg2+) is bound with phosphometabolites, nucleic acids, and proteins in eukaryotes. Little is known about the intracellular compartmentalization and molecular details of Mg2+ transport into/from cellular organelles such as the endoplasmic reticulum (ER). We found that the ER is a major iMg2+ 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 ERMg2+ uptake. Experiments reveal that a tyrosine residue is crucial for Mg2+ binding and activity in a mechanism conserved in both prokaryotic (mgtB and mgtA) and eukaryotic Mg2+ ATPases. Cardiac dysfunction by haploinsufficiency, abnormal Ca2+ cycling in mouse Erma+/- cardiomyocytes, and ERMA mRNA silencing in human iPSC-cardiomyocytes collectively define ERMA as an essential component of ERMg2+ uptake in eukaryotes.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Adenosine Triphosphatases
/
P-type ATPases
Limits:
Animals
/
Humans
Language:
En
Journal:
Mol Cell
/
Mol. cell
/
Molecular cell
Journal subject:
BIOLOGIA MOLECULAR
Year:
2024
Type:
Article
Affiliation country:
United States