Endoplasmic Reticulum Stress Delays Choroid Development in the HCAR1 Knockout Mouse.

The subretina, composed of the choroid and the retinal pigment epithelium (RPE), plays a critical role in proper vision. In addition to phagocytosis of photoreceptor debris, the RPE shuttles oxygen and nutrients to the neuroretina. For their own energy production, RPE cells mainly rely on lactate, a major by-product of glycolysis.

Disentangling the nonmetabolic roles of metabolites: lactate as a case study.

Many metabolites possess covalent and noncovalent signaling functions. However, ongoing research considers them mostly as ligands, neglecting their potential involvement in post-translational modifications. In this forum article, we discuss the dual signaling functions of metabolites, using lactate as a case study, and advocate for the use of multiple complementary techniques to disentangle their functions.

Novel Function of Nogo-A as Negative Regulator of Endothelial Progenitor Cell Angiogenic Activity: Impact in Oxygen-Induced Retinopathy.

Endothelial Progenitor Cells (EPCs) can actively participate in revascularization in oxygen-induced retinopathy (OIR). Yet the mechanisms responsible for their dysfunction is unclear. Nogo-A, whose function is traditionally related to the inhibition of neurite function in the central nervous system, has recently been documented to display anti-angiogenic pro-repellent properties.

The Succinate Receptor SUCNR1 Resides at the Endoplasmic Reticulum and Relocates to the Plasma Membrane in Hypoxic Conditions.

The GPCR SUCNR1/GPR91 exerts proangiogenesis upon stimulation with the Krebs cycle metabolite succinate. GPCR signaling depends on the surrounding environment and intracellular localization through location bias. Here, we show by microscopy and by cell fractionation that in neurons, SUCNR1 resides at the endoplasmic reticulum (ER), while being fully functional, as shown by calcium release and the induction of the expression of the proangiogenic gene for VEGFA.

Telomerase biogenesis requires a novel Mex67 function and a cytoplasmic association with the Sm complex.

The templating RNA is the core of the telomerase reverse transcriptase. In , the complex life cycle and maturation of telomerase includes a cytoplasmic stage. However, timing and reason for this cytoplasmic passage are poorly understood.

PRC2-Associated Chromatin Contacts in the Developing Limb Reveal a Possible Mechanism for the Atypical Role of PRC2 in HoxA Gene Expression.

Preventing inappropriate gene expression in time and space is as fundamental as triggering the activation of tissue- or cell-type-specific factors at the correct developmental stage and in the correct cells. Here, we study the impact of Polycomb repressive complex 2 (PRC2) function on HoxA gene regulation. We analyze chromatin conformation of the HoxA cluster and its regulatory regions and show that in addition to the well-known role of PRC2 in silencing Hox genes via direct binding, its function is required for the changes in HoxA long-range interactions distinguishing proximal limbs from distal limbs.

A Single Templating RNA in Yeast Telomerase.

The number of essential telomerase components in the active ribonucleoprotein (RNP) has important implications for its mechanism of action yet is by and large unknown. We report that two differentially tagged TLC1 RNAs endogenously expressed in a heterozygous diploid and simultaneously detected via multi-color fluorescence in situ hybridization (FISH) experiments do not co-localize. Probabilistic calculations combined with direct quantification of FISH signals demonstrate that the TLC1 RNA indeed occurs as a single molecule in these RNPs.