Endocytosis of G Protein-Coupled Receptors and Their Ligands: Is There a Role in Metal Trafficking?

The prevalence of metal dysregulation in many neurodegenerative and neurocognitive disorders has compelled many studying such diseases to investigate the mechanisms underlying metal regulation in the central nervous system. Metal homoeostasis is often complex, with sophisticated, multilayered pathways in operation. G protein-coupled receptors are omnipresent on cell membranes and have intriguing mechanisms of endocytosis and trafficking that may be useful in metal homoeostasis. Indeed, many receptors and/or their cognate ligands are able to bind metals, and in many cases metals are considered to have neuromodulatory roles as a result of receptor binding. In this mini-review, we outline the structural and functional aspects of G protein-coupled receptors with a focus on the mechanisms leading to endocytosis and cellular trafficking. We further highlight how this may help in the trafficking of metal ions, notably copper.     

Soil water content variability drives productivity responses of a model grassland system to extreme rainfall events under elevated CO<Subscript>2</Subscript>

Climate change is significantly altering rainfall patterns globally and will likely cause increases in extreme rainfall events. Grassland systems are particularly vulnerable to these changes as their productivity is strongly mediated by soil water content (SWC). SWC mean and variability are driven by the amount of rainfall received as well as the distribution through time of that rainfall. In this study, we used a model grassland system in a controlled glasshouse experiment to identify whether SWC mean or variability is a stronger driver of productivity. We then examined how extreme rainfall events alter this driver and the resulting effect this has on productivity and biomass allocation under ambient and elevated carbon dioxide (CO₂). Rainfall amount was held constant, but distribution through time varied (control, one in 20 years event, one in 100 years event). SWC variability was a stronger driver of productivity (mesocosm biomass) than SWC mean, with increasing extreme rainfall event magnitude resulting in greater SWC variability. Surprisingly, elevated CO₂ only had a small effect on these productivity and biomass allocation responses which may be due to the relatively small CO₂ difference tested. Our results suggest that distribution of rainfall in time is an important driver of grassland productivity and that increases in extreme rainfall events, for a given total rainfall, will result in reduced grassland productivity.     

Villainous role of estrogen in macrophage-nerve interaction in endometriosis

Endometriosis is a complex and heterogeneous disorder with unknown etiology. Dysregulation of macrophages and innervation are important factors influencing the pathogenesis of endometriosis-associated pain. It is known to be an estrogen-dependent disease, estrogen can promote secretion of chemokines from peripheral nerves, enhancing the recruitment and polarization of macrophages in endometriotic tissue. Macrophages have a role in the expression of multiple nerve growth factors (NGF), which mediates the imbalance of neurogenesis in an estrogen-dependent manner. Under the influence of estrogen, co-existence of macrophages and nerves induces an innovative neuro-immune communication. Persistent stimulation by inflammatory cytokines from macrophages on nociceptors of peripheral nerves aggravates neuroinflammation through the release of inflammatory neurotransmitters. This neuro-immune interaction regulated by estrogen sensitizes peripheral nerves, leading to neuropathic pain in endometriosis. The aim of this review is to highlight the significance of estrogen in the interaction between macrophages and nerve fibers, and to suggest a potentially valuable therapeutic target for endometriosis-associated pain.