An update of the Worldwide Integrated Assessment (WIA) on systemic insecticides. Part 2: impacts on organisms and ecosystems

New information on the lethal and sublethal effects of neonicotinoids and fipronil on organisms is presented in this review, complementing the previous WIA in 2015. The high toxicity of these systemic insecticides to invertebrates has been confirmed and expanded to include more species and compounds. Most of the recent research has focused on bees and the sublethal and ecological impacts these insecticides have on pollinators. Toxic effects on other invertebrate taxa also covered predatory and parasitoid natural enemies and aquatic arthropods. Little, while not much new information has been gathered on soil organisms. The impact on marine coastal ecosystems is still largely uncharted. The chronic lethality of neonicotinoids to insects and crustaceans, and the strengthened evidence that these chemicals also impair the immune system and reproduction, highlights the dangers of this particular insecticidal classneonicotinoids and fipronil. , withContinued large scale – mostly prophylactic – use of these persistent organochlorine pesticides has the potential to greatly decreasecompletely eliminate populations of arthropods in both terrestrial and aquatic environments. Sublethal effects on fish, reptiles, frogs, birds and mammals are also reported, showing a better understanding of the mechanisms of toxicity of these insecticides in vertebrates, and their deleterious impacts on growth, reproduction and neurobehaviour of most of the species tested. This review concludes with a summary of impacts on the ecosystem services and functioning, particularly on pollination, soil biota and aquatic invertebrate communities, thus reinforcing the previous WIA conclusions (van der Sluijs et al. 2015)

Structure and Function of the Cochaperone Prefoldin

Molecular chaperones are key players in proteostasis, the balance between protein synthesis, folding, assembly and degradation. They are helped by a plethora of cofactors termed cochaperones, which direct chaperones towards any of these different, sometime opposite pathways. One of these is prefoldin (PFD), present in eukaryotes and in archaea, a heterohexamer whose best known role is the assistance to group II chaperonins (the Hsp60 chaperones found in archaea and the eukaryotic cytosolic) in the folding of proteins in the cytosol, in particular cytoskeletal proteins. However, over the last years it has become evident a more complex role for this cochaperone, as it can adopt different oligomeric structures, form complexes with other proteins and be involved in many other processes, both in the cytosol and in the nucleus, different from folding. This review intends to describe the structure and the many functions of this interesting macromolecular complex

Role of the Unconventional Prefoldin Proteins URI and UXT in Transcription Regulation

The Unconventional prefoldin RPB5 interacting protein (URI), also known as RPB5-Mediating Protein (RMP) has been shown to play several regulatory roles in different cellular compartments including the mitochondria, as a phosphatase binding protein; in the cytoplasm, as a chaperone-like protein; and in the nucleus, as a transcriptional regulator through binding to RPB5 and RNA polymerase II (polII). This chapter focuses on the role URI plays in transcriptional regulation in the prostate cell. In prostate cells, URI is tightly bound to another prefoldin-like protein called UXT, a known androgen receptor (AR) cofactor. Part of a multiprotein complex, URI and UXT act as transcriptional repressors, and URI regulates KAP1 through PP2A phosphatase activity. The discovery of the interaction of URI and UXT with KAP1, AR, and PP2A, as well as the numerous interactions between URI and components of the R2TP/prefoldin-like complex, RPB5, and nuclear proteins involved in DNA damage response, chromatin remodeling and gene transcription, reveal a pleiotropic effect of the URI/UXT complex on nuclear processes. The mechanisms by which URI/UXT affect transcription, chromatin structure and regulation, and genome stability, remain to be elucidated but will be of fundamental importance considering the many processes affected by alterations of URI/UXT and other prefoldins and prefoldin-like proteins

Spindle assembly requires complete disassembly of spindle remnants from the previous cell cycle

Incomplete spindle disassembly causes lethality in budding yeast. We propose that spindle disassembly is required to reinitiate the spindle cycle during the subsequent mitosis by regenerating the nuclear pool of assembly-competent tubulin

Functional Contributions of Prefoldin to Gene Expression

Prefoldin is a co-chaperone that evolutionarily originates in archaea, is universally present in all eukaryotes and acts as a co-chaperone by facilitating the supply of unfolded or partially folded substrates to class II chaperonins. Eukaryotic prefoldin is known mainly for its functional relevance in the cytoplasmic folding of actin and tubulin monomers during cytoskeleton assembly. However, the role of prefoldin in chaperonin-mediated folding is not restricted to cytoskeleton components, but extends to both the assembly of other cytoplasmic complexes and the maintenance of functional proteins by avoiding protein aggregation and facilitating proteolytic degradation. Evolution has favoured the diversification of prefoldin subunits, and has allowed the so-called prefoldin-like complex, with specialised functions, to appear. Subunits of both canonical and prefoldin-like complexes have also been found in the nucleus of yeast and metazoan cells, where they have been functionally connected with different gene expression steps. Plant prefoldin has also been detected in the nucleus and is physically associated with a gene regulator. Here we summarise information available on the functional involvement of prefoldin in gene expression, and discuss the implications of these results for the relationship between prefoldin structure and function