ERMA (TMEM94) is a P-type ATPase transporter for Mg2+ uptake in the endoplasmic reticulum.

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.

Variable Creatinine Levels in Critical Care Patients: A Concerning Knowledge Gap.

An accurate creatinine (Cr) estimate is pivotal for the assessment of renal function. Both patient- and practice-spawned factors palliate the test accuracy of serum creatinine (sCr) and can erratically represent actual kidney function. This study evaluated the caregivers' awareness of enzymatic serum creatinine (E-sCr) assay interfering in dopamine/dobutamine (DD)-infused patient samples and the frequency of such interference in a critical care setting. We conducted an sCr awareness survey among UT Southwestern physicians, nurses, and pharmacists. We then performed a cross-sectional E-sCr comparison against the kinetic Jaffe method using the DD-infused patient samples collected from central venous catheters (CVC), peripherally inserted central catheter (PICC) lines, and the peripheral vein (PV). We retrospectively compared the longitudinal E-sCr results of the CVC/PICC draws with the corresponding blood urea nitrogen (BUN) levels. The survey results show a significant lack of awareness among caregivers about the negative interference of DD infusions on E-sCr. Cross-sectional E-sCr assessment relative to the Jaffe method displayed a negative interference in 12% of CVC/PICC line samples (7/57 DD-infused patients) compared to none in the PV draws. A longitudinal assessment of E-sCr, BUN, and potassium (K) levels from CVC/PICC line samples further confirmed a spurious decrease for E-sCr in about 12/50 (24%) patients who did not show a concurrent BUN or K decrease. The results suggest that a direct PV sampling accompanied by clinical laboratory-directed proactive discussion/activities can foster awareness among caregivers and eschew the false E-sCr estimates in DD-infused patients.