Localizing PRL-2 expression and determining the effects of dietary Mg2+ on expression levels

Abstract

The phosphatase of regenerating liver (PRL) is a group of protein tyrosine phosphatases that play a key role in cancer progression and metastasis. We previously showed that PRL-2 modulates intracellular Mg(2+) levels and sustains cancer phenotypes by binding to the Mg(2+) transporter CNNM3. However, the physiological functions of PRL-2 in animals remain largely unknown. To better understand which cell types are associated with PRL-2 function, we characterized its expression in mouse tissues using a PRL-2 β-galactosidase reporter mouse model. Our results demonstrated that PRL-2 was ubiquitously expressed, with the highest expression levels observed in the hippocampal pyramidal neurons, ependymal cells, cone and rod photoreceptor cells, endocardium, vascular and bronchial smooth muscle, and collecting ducts in the kidney. On the other hand, PRL-2 expression was undetectable or very low in the parenchymal cells of the liver and pancreas. Our results also indicated that PRL-2 is involved in cell-type-specific Mg(2+) homeostasis and that PRL-2 expression is potentially inversely regulated by dietary Mg(2+) levels.

Physiological and oncogenic roles of the PRL phosphatases

“…Expression of the PRLs follows a magnesium‐dependent circadian pattern and a mouse knockout of PRL‐2 highlights a key role for this phosphatase in circadian control of behavior and metabolism . These observations are consistent with the regulation of PRLs expression by extracellular magnesium levels in multiple cell lines and also in vivo by dietary magnesium in a PRL‐2 reporter mouse models , thus establishing the PRLs as important regulators of magnesium homeostasis.…”

PRL2 links magnesium flux and sex-dependent circadian metabolic rhythms

“…Cryosections were prepared at 20-μm thickness for X-gal staining and 10-μm thickness for immunofluorescence. X-gal tissue staining was performed as described previously (17). For immunofluorescence, frozen sections were fixed with ice-cold methanol for 10 minutes.…”

“…are quite high (13), yet each PRL protein exhibits distinct tissue expression levels and patterns (14)(15)(16)(17). These results suggest that, through evolution, each PRL has acquired divergent physiological functions in animals.…”

“…These results suggest that, through evolution, each PRL has acquired divergent physiological functions in animals. Among the 3 PRLs, PRL2 is the most ubiquitously expressed in mammals (15,17). Moreover, analysis of PRL2-deficient mice revealed that PRL2 is required for proper placental development (18), spermatogenesis (19), and hematopoietic stem cell self-renewal (20).…”

PRL-1 is required for neuroprotection against olfactory CO2 stimulation in Drosophila

“…Characterization of the Prl family members has been conducted for early embryos of Drosophila, amphioxus and zebrafish, where Prls were seen to be uniformly expressed in the central nervous system (CNS) and suggested to be likely involved in early neural development (Lin, Lee et al, 2013). In a mouse model PRL-2 was noted as ubiquitously expressed, particularly in the hippocampal pyramidal neurons, ependymal cells, cone and rod photoreceptor cells (Gungabeesoon, Tremblay et al, 2016). We initially investigated the function of Drosophila Prl-1 by generation of prl-1 mutant using CRISPR/Cas9 method (Bassett & Liu, 2014, Bassett, Tibbit et al, 2013.…”