Phosphorylation of STIM1 at ERK/CDK sites is dispensable for cell migration and ER partitioning in mitosis.

Store-operated Ca2+ entry (SOCE) is a ubiquitous Ca2+ influx pathway required for multiple physiological functions including cell motility. SOCE is triggered in response to depletion of intracellular Ca2+ stores following the activation of the endoplasmic reticulum (ER) Ca2+ sensor STIM1, which recruits the plasma membrane (PM) Ca2+ channel Orai1 at ER-PM junctions. STIM1 is phosphorylated dynamically, and this phosphorylation has been implicated in several processes including SOCE inactivation during M-phase, maximal SOCE activation, ER segregation during mitosis, and cell migration. Human STIM1 has 10 Ser/Thr residues in its cytosolic domain that match the ERK/CDK consensus phosphorylation. We recently generated a mouse knock-in line where wild-type STIM1 was replaced by a non-phosphorylatable STIM1 with all ten S/Ts mutated to Ala (STIM1-10A). Here, we generate mouse embryonic fibroblasts (MEF) from the STIM1-10A mouse line and a control MEF line (WT) that express wild-type STIM1 from a congenic mouse strain. These lines offer a unique model to address the role of STIM1 phosphorylation at endogenous expression levels in contrast to previous studies that relied mostly on overexpression. We show that STIM1 phosphorylation at ERK/CDK sites is not required for SOCE activation, cell migration, or ER partitioning during mitosis. These results rule out STIM1 phosphorylation as a regulator of SOCE, migration, and ER distribution in mitosis.

The epidemiology of hepatitis C virus in Central Asia: Systematic review, meta-analyses, and meta-regression analyses.

The objective was to delineate hepatitis C virus (HCV) epidemiology in countries of Central Asia (CA), specifically Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan. A systematic review was conducted guided by the Cochrane Collaboration Handbook, and reported using PRISMA guidelines. Meta-analyses were performed using DerSimonian-Laird random-effects models with inverse variance weighting. Random-effects meta-regression analyses were performed on general population studies. The systematic review identified a total of 208 HCV prevalence measures. No incidence or Turkmenistan studies were identified. Meta-analyses estimated HCV prevalence among the general population at 0.7% (95%CI: 0.7-0.8%) in Kazakhstan, 2.0% (95%CI: 1.7-2.4%) in Kyrgyzstan, 2.6% (95%CI: 1.7-3.6%) in Tajikistan, and 9.6 (95%CI: 5.8-14.2%) in Uzbekistan. Across CA, the pooled mean prevalence was 13.5% (95%CI: 10.9-16.4%) among non-specific clinical populations, 31.6% (95%CI: 25.8-37.7%) among populations with liver-related conditions, and 51.3% (95%CI: 46.9-55.6%) among people who inject drugs. Genotypes 1 (52.6%) and 3 (38.0%) were most frequent. Evidence was found for statistically-significant differences in prevalence by country, but not for a temporal decline in prevalence. CA is one of the most affected regions by HCV infection with Uzbekistan enduring one of the highest prevalence levels worldwide. Ongoing HCV transmission seems to be driven by injecting drug use and healthcare exposures.