The immutans (im) mutant of Arabidopsis shows a variegated phenotype comprising albino and green somatic sectors. We have cloned the IM gene by transposon tagging and show that even stable null alleles give rise to a variegated phenotype. The gene product has amino acid similarity to the mitochondrial alternative oxidase. We show that the IM protein is synthesized as a precursor polypeptide that is imported into chloroplasts and inserted into the thylakoid membrane. The albino sectors of im plants contain reduced levels of carotenoids and increased levels of the caro-tenoid precursor phytoene. The data presented here are consistent with a role for the IM protein as a cofactor for caro-tenoid desaturation. The suggested terminal oxidase function of IM appears to be essential to prevent photooxidative damage during early steps of chloroplast formation. We propose a model in which IM function is linked to phytoene de-saturation and, possibly, to the respiratory activity of the chloroplast.
NALP1 is a member of the NOD-like receptor (NLR) family of proteins that form inflammasomes. Upon cellular infection or stress, inflammasomes are activated, triggering maturation of proinflammatory cytokines and downstream cellular signaling mediated through the MyD88 adaptor. Toxoplasma gondii is an obligate intracellular parasite that stimulates production of high levels of proinflammatory cytokines that are important in innate immunity. In this study, susceptibility alleles for human congenital toxoplasmosis were identified in the NALP1 gene. To investigate the role of the NALP1 inflammasome during infection with T. gondii, we genetically engineered a human monocytic cell line for NALP1 gene knockdown by RNA interference. NALP1 silencing attenuated progression of T. gondii infection, with accelerated host cell death and eventual cell disintegration. In line with this observation, upregulation of the proinflammatory cytokines interleukin-1 (IL-1), IL-18, and IL-12 upon T. gondii infection was not observed in monocytic cells with NALP1 knockdown. These findings suggest that the NALP1 inflammasome is critical for mediating innate immune responses to T. gondii infection and pathogenesis. Although there have been recent advances in understanding the potent activity of inflammasomes in directing innate immune responses to disease, this is the first report, to our knowledge, on the crucial role of the NALP1 inflammasome in the pathogenesis of T. gondii infections in humans.
The immutans ( im ) mutant of Arabidopsis shows a variegated phenotype comprising albino and green somatic sectors. We have cloned the IM gene by transposon tagging and show that even stable null alleles give rise to a variegated phenotype. The gene product has amino acid similarity to the mitochondrial alternative oxidase. We show that the IM protein is synthesized as a precursor polypeptide that is imported into chloroplasts and inserted into the thylakoid membrane. The albino sectors of im plants contain reduced levels of carotenoids and increased levels of the carotenoid precursor phytoene. The data presented here are consistent with a role for the IM protein as a cofactor for carotenoid desaturation. The suggested terminal oxidase function of IM appears to be essential to prevent photooxidative damage during early steps of chloroplast formation. We propose a model in which IM function is linked to phytoene desaturation and, possibly, to the respiratory activity of the chloroplast. INTRODUCTIONIn plant cells, plastid differentiation is intimately linked to organogenesis and is affected by both developmental regulatory mechanisms and environmental conditions. The complex mechanisms involved in the phototransformation of the plastids of dark-grown seedlings (etioplasts) to photosynthetically active plastids (chloroplasts) have been described extensively (reviewed in Mullet, 1988;Taylor, 1989;Chory and Susek, 1994). Alternatively, developing grass tissues provide a unique system in which a gradient of developmental stages of cells and plastids (proplastids to chloroplasts) is present (Mullet, 1988;Bilang and Bogorad, 1996; Inada et al., 1996).Mutants visibly impaired in chloroplast differentiation can be selected by their pale green, yellow, or albino color. The chlorophyll-deficient mutant olive of Antirrhinum has this phenotype (Hudson et al., 1993). Not all of these mutants are altered directly in pigment synthesis. Putative functions can be proposed for mutated genes based on the similarity of their coding sequences to known proteins. The Arabidopsis mutant albino3 (Sundberg et al., 1997) is impaired in chloroplast membrane biogenesis, as suggested by amino acid sequence similarity between ALBINO3 and the yeast mitochondrial OXA1 protein involved in mitochondrial biogenesis. The Arabidopsis cla1 mutation (Mandel et al., 1996) identifies an enzyme also present in cyanobacteria. Mutations also have been described that affect the proplastid-tochloroplast transition. The dag mutant from Antirrhinum (Chatterjee et al., 1996) and dcl1 from tomato (Keddie et al., 1996) do not contain chloroplasts but rather plastids resembling nondifferentiated proplastids. These genes together with the PALE CRESS gene from Arabidopsis (Reiter et al., 1994) affect both chloroplast development and leaf architecture.One class of mutations gives rise to variegated plants that have a mutant phenotype in some sectors and a wild-type phenotype in others. The iojap (Han et al., 1992) mutant of maize or the chloroplast mutator in ma...
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