Endogenous L- to D-amino acid residue isomerization modulates selectivity between distinct neuropeptide receptor family members

The L- to D-amino acid residue isomerization of neuropeptides is an understudied post-translational modification found in animals across several phyla. Despite its physiological importance, little information is available regarding the impact of endogenous peptide isomerization on receptor recognition and activation. As a result, the full roles peptide isomerization play in biology are not well understood. Here, we identify that the Aplysia allatotropin-related peptide (ATRP) signaling system utilizes L- to D-residue isomerization of one amino acid residue in the neuropeptide ligand to modulate selectivity between two distinct G protein-coupled receptors (GPCRs). We first identified a novel receptor for ATRP that is selective for the D2-ATRP form, which bears a single D-phenylalanine residue at position 2. Using cell-based receptor activation experiments, we then characterized the stereoselectivity of the two known ATRP receptors for both endogenous ATRP diastereomers, as well as for homologous toxin peptides from a carnivorous predator. We found that the ATRP system displayed dual signaling through both the Gαq and Gαs pathways, and each receptor was selectively activated by one naturally occurring ligand diastereomer over the other. Overall, our results provide insights into an unexplored mechanism by which nature regulates intercellular communication. Given the challenges in detecting L- to D-residue isomerization from complex mixtures de novo and in identifying receptors for novel neuropeptides, it is likely that other neuropeptide-receptor systems may also utilize changes in stereochemistry to modulate receptor selectivity in a manner similar to that discovered here

Sectoral approaches to improve regional carbon budgets

Humans utilise about 40% of the earth’s net primary production (NPP) but the products of this NPP are often managed by different sectors, with timber and forest products managed by the forestry sector and food and fibre products from croplands and grasslands managed by the agricultural sector. Other significant anthropogenic impacts on the global carbon cycle include human utilization of fossil fuels and impacts on less intensively managed systems such as peatlands, wetlands and permafrost. A great deal of knowledge, expertise and data is available within each sector. We describe the contribution of sectoral carbon budgets to our understanding of the global carbon cycle. Whilst many sectors exhibit similarities for carbon budgeting, some key differences arise due to differences in goods and services provided, ecology, management practices used, landmanagement personnel responsible, policies affecting land management, data types and availability, and the drivers of change. We review the methods and data sources available for assessing sectoral carbon budgets, and describe some of key data limitations and uncertainties for each sector in different regions of the world. We identify the main gaps in our knowledge/data, show that coverage is better for the developed world for most sectors, and suggest how sectoral carbon budgets could be improved in the future. Research priorities include the development of shared protocols through site networks, a move to full carbon accounting within sectors, and the assessment of full greenhouse gas budgets