Synthesising plausible futures for biodiversity and ecosystem services in Europe and Central Asia using scenario archetypes

Scenarios are a useful tool to explore possible futures of social-ecological systems. The number of scenarios has increased dramatically over recent decades, with a large diversity in temporal and spatial scales, purposes, themes, development methods, and content. Scenario archetypes generically describe future developments and can be useful in meaningfully classifying scenarios, structuring and summarizing the overwhelming amount of information, and enabling scientific outputs to more effectively interface with decision-making frameworks. The Intergovernmental Platform for Biodiversity and Ecosystem Services (IPBES) faced this challenge and used scenario archetypes in its assessment of future interactions between nature and society. We describe the use of scenario archetypes in the IPBES Regional Assessment of Europe and Central Asia. Six scenario archetypes for the region are described in terms of their driver assumptions and impacts on nature (including biodiversity) and its contributions to people (including ecosystem services): business-as-usual, economic optimism, regional competition, regional sustainability, global sustainable development, and inequality. The analysis shows that trade-offs between nature’s contributions to people are projected under different scenario archetypes. However, the means of resolving these trade-offs depend on differing political and societal value judgements within each scenario archetype. Scenarios that include proactive decision making on environmental issues, environmental management approaches that support multifunctionality, and mainstreaming environmental issues across sectors, are generally more successful in mitigating trade-offs than isolated environmental policies. Furthermore, those scenario archetypes that focus on achieving a balanced supply of nature’s contributions to people and that incorporate a diversity of values are estimated to achieve more policy goals and targets, such as the UN Sustainable Development Goals and the Convention on Biological Diversity Aichi targets. The scenario archetypes approach is shown to be helpful in supporting science-policy dialogue for proactive decision making that anticipates change, mitigates undesirable trade-offs, and fosters societal transformation in pursuit of sustainable development

Regulation of Focal Adhesion Kinase by a Novel Protein Inhibitor FIP200

Focal adhesion kinase (FAK) is a major mediator of integrin signaling pathways. The mechanisms of regulation of FAK activity and its associated cellular functions are not very well understood. Here, we present data suggesting that a novel protein FIP200 functions as an inhibitor for FAK. We show the association of endogenous FIP200 with FAK, which is decreased upon integrin-mediated cell adhesion concomitant with FAK activation. In vitro- and in vivo-binding studies indicate that FIP200 interacts with FAK through multiple domains directly. FIP200 bound to the kinase domain of FAK inhibited its kinase activity in vitro and its autophosphorylation in vivo. Overexpression of FIP200 or its segments inhibited cell spreading, cell migration, and cell cycle progression, which correlated with their inhibition of FAK activity in vivo. The inhibition of these cellular functions by FIP200 could be rescued by coexpression of FAK. Last, we show that disruption of the functional interaction between endogenous FIP200 with FAK leads to increased FAK phosphorylation and partial restoration of cell cycle progression in cells plated on poly-l-lysine, providing further support for FIP200 as a negative regulator of FAK. Together, these results identify FIP200 as a novel protein inhibitor for FAK

Paxillin-dependent Paxillin Kinase Linker and p21-Activated Kinase Localization to Focal Adhesions Involves a Multistep Activation Pathway

The precise temporal-spatial regulation of the p21-activated serine-threonine kinase PAK at the plasma membrane is required for proper cytoskeletal reorganization and cell motility. However, the mechanism by which PAK localizes to focal adhesions has not yet been elucidated. Indirect binding of PAK to the focal adhesion protein paxillin via the Arf-GAP protein paxillin kinase linker (PKL) and PIX/Cool suggested a mechanism. In this report, we demonstrate an essential role for a paxillin–PKL interaction in the recruitment of activated PAK to focal adhesions. Similar to PAK, expression of activated Cdc42 and Rac1, but not RhoA, stimulated the translocation of PKL from a generally diffuse localization to focal adhesions. Expression of the PAK regulatory domain (PAK1–329) or the autoinhibitory domain (AID 83–149) induced PKL, PIX, and PAK localization to focal adhesions, indicating a role for PAK scaffold activation. We show PIX, but not NCK, binding to PAK is necessary for efficient focal adhesion localization of PAK and PKL, consistent with a PAK–PIX–PKL linkage. Although PAK activation is required, it is not sufficient for localization. The PKL amino terminus, containing the PIX-binding site, but lacking paxillin-binding subdomain 2 (PBS2), was unable to localize to focal adhesions and also abrogated PAK localization. An identical result was obtained after PKLΔPBS2 expression. Finally, neither PAK nor PKL was capable of localizing to focal adhesions in cells overexpressing paxillinΔLD4, confirming a requirement for this motif in recruitment of the PAK–PIX–PKL complex to focal adhesions. These results suggest a GTP-Cdc42/GTP-Rac triggered multistep activation cascade leading to the stimulation of the adaptor function of PAK, which through interaction with PIX provokes a functional PKL PBS2–paxillin LD4 association and consequent recruitment to focal adhesions. This mechanism is probably critical for the correct subcellular positioning of PAK, thereby influencing the ability of PAK to coordinate cytoskeletal reorganization associated with changes in cell shape and motility