Tonoplast Inositol Transporters: Roles in Plant Abiotic Stress Response and Crosstalk with Other Signals

Inositol transporter (INT) is reputed as the pivotal transporter for vital metabolites like lipids, minerals, and sugars particularly. These transporters play important role in transitional metabolism and various signaling pathways in plants through regulating the transduction of messages from hormones, neurotransmitters, and immunologic and growth factors. Extensive studies have been conducted on animal INT with promising outcomes. However, few recent studies have highlighted the importance and the complexity of INT genes in the regulation of plant physiology stages including growth and tolerance to stress conditions. The present review sum-up the most recent findings on the role of INT or inositol genes in plant metabolisms and the responsive mechanisms that cope with external stressors. Moreover, we highlighted the emerging role of vacuoles and vacuolar inositol transporters in plant molecular transition and their related roles in plant growth and development. Inositol transporters are the essential mediator for the inositol uptake and its intracellular broadcasting for various metabolic pathways where they play crucial roles. Also, so far characterized only in animals, we reported evidence on Na+/inositol transporters H+/inositol symporters and suggested their roles and operating mode in plants. Thus, understanding the INT functioning system, the coordinated movement of inositol, and the relation between inositol generation and other important plant signaling pathways would be an excellent asset for advancement in researches on plant stress adaptation.

Finding the Sweet Spot: How Human Fungal Pathogens Acquire and Turn the Sugar Inositol against Their Hosts

ABSTRACTInositol is an essential nutrient with important structural and signaling functions in eukaryotes. Its role in microbial pathogenesis has been reported in fungi, protozoans, and eubacteria. In a recent article, Porollo et al. [mBio5(6):e01834-14, 2014, doi:10.1128/mBio.01834-14] demonstrated the importance of inositol metabolism in the development and viability of Pneumocystis species—obligate fungal pathogens that remain unculturablein vitro. To understand their obligate nature, the authors used innovative comparative genomic approaches and discovered that Pneumocystis spp. are inositol auxotrophs due to the lack of inositol biosynthetic enzymes and that inositol insufficiency is a contributing factor preventing fungal growthin vitro. This work is in accord with other studies suggesting that inositol plays a conserved role in microbial pathogenesis. Inositol uptake and metabolism therefore may represent novel antimicrobial drug targets. Using comparative genomics to analyze metabolic pathways offers a powerful tool to gain new insights into nutrient utilization in microbes, especially obligate pathogens.

Two Major Inositol Transporters and Their Role in Cryptococcal Virulence

ABSTRACTCryptococcus neoformansis an AIDS-associated human fungal pathogen and the most common cause of fungal meningitis, with a mortality rate over 40% in AIDS patients. Significant advances have been achieved in understanding its disease mechanisms. Yet the underlying mechanism of a high frequency of cryptococcal meningitis remains unclear. The existence of high inositol concentrations in brain and our earlier discovery of a large inositol transporter (ITR) gene family inC. neoformansled us to investigate the potential role of inositol inCryptococcus-host interactions. In this study, we focus on functional analyses of two majorITRgenes to understand their role in virulence ofC. neoformans. Our results show thatITR1AandITR3Care the only twoITRgenes among 10 candidates that can complement the growth defect of aSaccharomyces cerevisiaestrain lacking inositol transporters. BothS. cerevisiaestrains heterologously expressingITR1AorITR3Cshowed high inositol uptake activity, an indication that they are major inositol transporters. Significantly,itr1a itr3cdouble mutants showed significant virulence attenuation in murine infection models. Mutating bothITR1AandITR3Cin anino1mutant background activates the expression of several remainingITRcandidates and does not show more severe virulence attenuation, suggesting that both inositol uptake and biosynthetic pathways are important for inositol acquisition. Overall, our study provides evidence that host inositol and fungal inositol transporters are important forCryptococcuspathogenicity.

Role of integrin α1β1 in the regulation of renal medullary osmolyte concentration

The mechanism by which cells sense extracellular tonicity and trigger the accumulation of protective organic osmolytes is poorly understood. It has been proposed that changes in cell volume following alteration of extracellular toncity are important initiators of signaling events that lead to osmolyte accumulation. Because the extracellular matrix receptors integrins are linked to the cytoskeleton and can transduce signals that alter cell behavior, we investigated the role of these receptors in the modulation of osmolyte accumulation in the kidney medulla under different osmotic conditions. We show that integrin α1-null mice have impaired ability to accumulate organic osmolytes in the inner medulla due to altered signaling and decreased induction of osmolyte transporters or aldose reductase gene transcription. Utilizing inner medullary collecting duct cells, we demonstrate that the lack of integrin α1β1 results in an impaired ability to induce the tonicity enhancer-binding protein TonEBP under hypertonic conditions. Furthermore, under the same conditions, integrin α1-null cells show prolonged ERK1/2 phosphorylation and decreased inositol uptake compared with control cells. The reduction of inositol uptake is significantly reversed by treatment with the MEK inhibitor PD-98059. Finally, integrin α1-null mice develop morphological changes of early tubular necrosis and increased apoptosis of renal medullary cells following dehydration. Together, these results show that integrin α1β1 is an important mediator of the compatible osmolyte response in the medulla of the mammalian kidney.

Inositol transport in mouse embryonic stem cells

The uptake of myo-inositol by mouse embryonic stem (ES) cells was measured using [2-3H]myo-inositol. Uptake of myo-inositol by ES cells occurred in a mainly saturable, sodium-, time- and temperature-dependent manner, which was inhibited by glucose, phloridzin and ouabain. Self inhibition by inositol was much greater than inhibition by glucose indicating that transport was not occurring via a sodium-dependent glucose transporter. Uptake rate was much greater than efflux rate indicating a mainly unidirectional transport mechanism. Estimated kinetics parameters for sodium-dependent inositol uptake were a Km of 65.1 ± 11.8 μ mol L−1 and a Vmax of 5.0 ± 0.59 pmol μ g protein−1 h−1. Inositol uptake was also sensitive to osmolality; uptake increased in response to incubation in hypertonic medium indicating a possible role for inositol as an osmolyte in ES cells. These characteristics indicate that myo-inositol transport in mouse ES cells occurs by a sodium-dependent myo-inositol transporter protein.