SummaryArsenic and selenium are metalloids found in the environment. Arsenic is considered to pose the most significant potential threat to human health based on frequency of occurrence, toxicity and human exposure. Selenium, on the other hand, ranks only 147 th in toxicity but, in contrast to arsenic, is also a required micronutrient. Whether a toxin or micronutrient, their metabolism requires that cells to accumulate these metalloids. In this review we discuss the membrane proteins that transport arsenic and selenium into cells, from bacteria to humans, as well as some the efflux proteins involved in detoxification.

NS, Terada LS, Nwariaku FE. Regulation of VEGF-induced endothelial cell migration by mitochondrial reactive oxygen species.

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Rice accumulates high level of arsenic (As) in its edible parts and thus plays an important role in the transfer of As into the food chain. However, the mechanisms of As uptake and its detoxification in rice are not well understood. Recently, members of the Nodulin 26-like intrinsic protein (NIP) subfamily of plant aquaporins were shown to transport arsenite in rice and Arabidopsis. Here we report that members of the rice plasma membrane intrinsic protein (PIP) subfamily are also involved in As tolerance and transport. Based on the homology search with the mammalian AQP9 and yeast Fps1 arsenite transporters, we identified and cloned five rice PIP gene subfamily members. qRT-PCR analysis of PIPs in rice root and shoot tissues revealed a significant down regulation of transcripts encoding OsPIP1;2, OsPIP1;3, OsPIP2;4, OsPIP2;6, and OsPIP2;7 in response to arsenite treatment. Heterologous expression of OsPIP2;4, OsPIP2;6, and OsPIP2;7 in Xenopus laevis oocytes significantly increased the uptake of arsenite. Overexpression of OsPIP2;4, OsPIP2;6, and OsPIP2;7 in Arabidopsis yielded enhanced arsenite tolerance and higher biomass accumulation. Further, these transgenic plants showed no significant accumulation of As in shoot and root tissues in long term uptake assays. Whereas, short duration exposure to arsenite caused both active influx and efflux of As in the roots. The data suggests a bidirectional arsenite permeability of rice PIPs in plants. These rice PIPs genes will be highly useful for engineering important food and biofuel crops for enhanced crop productivity on contaminated soils without increasing the accumulation of toxic As in the biomass or edible tissues.

SLC39A8 is an evolutionarily highly conserved gene that encodes the ZIP8 metal cation transporter in all vertebrates. SLC39A8 is ubiquitously expressed, including pluripotent embryonic stem cells; SLC39A8 expression occurs in every cell type examined. Uptake of ZIP8-mediated Mn2+, Zn2+, Fe2+, Se4+, and Co2+ represents endogenous functions—moving these cations into the cell. By way of mouse genetic differences, the phenotype of “subcutaneous cadmium-induced testicular necrosis” was assigned to the Cdm locus in the 1970s. This led to identification of the mouse Slc39a8 gene, its most closely related Slc39a14 gene, and creation of Slc39a8-overexpressing, Slc39a8(neo/neo) knockdown, and cell type-specific conditional knockout mouse lines; the Slc39a8(−/−) global knockout mouse is early-embryolethal. Slc39a8(neo/neo) hypomorphs die between gestational day 16.5 and postnatal day 1—exhibiting severe anemia, dysregulated hematopoiesis, hypoplastic spleen, dysorganogenesis, stunted growth, and hypomorphic limbs. Not surprisingly, genome-wide association studies subsequently revealed human SLC39A8-deficiency variants exhibiting striking pleiotropy—defects correlated with clinical disorders in virtually every organ, tissue, and cell-type: numerous developmental and congenital disorders, the immune system, cardiovascular system, kidney, lung, liver, coagulation system, central nervous system, musculoskeletal system, eye, and gastrointestinal tract. Traits with which SLC39A8-deficiency variants are currently associated include Mn2+-deficient hypoglycosylation; numerous birth defects; Leigh syndrome-like mitochondrial redox deficiency; decreased serum high-density lipoprotein-cholesterol levels; increased body mass index; greater risk of coronary artery disease, hypotension, cardiovascular death, allergy, ischemic stroke, schizophrenia, Parkinson disease, inflammatory bowel disease, Crohn disease, myopia, and adolescent idiopathic scoliosis; systemic lupus erythematosus with primary Sjögren syndrome; decreased height; and inadvertent participation in the inflammatory progression of osteoarthritis.