Sugar Transport Mechanism Research Articles

Glucose Transporter and Sensor Mechanisms in Fungal Pathogens as Potential Drug Targets.

Fungal infections are emerging as major health challenges in recent years. The development of resistance against existing antifungal agents needs urgent attention and action. The limited classes of antifungal drugs available, their tendency to cause adverse effects, lack of effectiveness, etc., are the major limitations of current therapy. Thus, there is a pressing demand for new antifungal drug classes to cope with the present circumstances. Glucose is the key source of energy for all organisms, including fungi. Glucose plays a crucial role as a source of carbon and energy for processes like virulence, growth, invasion, biofilm formation, and resistance development. The glucose transport and sensing mechanisms are well developed in these organisms as an important strategy to sustain survival. Modulating these transport or sensor mechanisms may serve as an important strategy to inhibit fungal growth. Moreover, the structural difference between human and fungal glucose transporters makes them more appealing as drug targets. Limited literature is available for fungal glucose entry mechanisms. This review provides a comprehensive account of sugar transport mechanisms in common fungal pathogens.

Soybean hypocotyl elongation is regulated by a MYB33-SWEET11/21-GA2ox8c module involving long-distance sucrose transport.

The length of hypocotyl affects the height of soybean and lodging resistance, thus determining the final grain yield. However, research on soybean hypocotyl length is scarce, and the regulatory mechanisms are not fully understood. Here, we identified a module controlling the transport of sucrose, where sucrose acts as a messenger moved from cotyledon to hypocotyl, regulating hypocotyl elongation. This module comprises four key genes, namely MYB33, SWEET11, SWEET21 and GA2ox8c in soybean. In cotyledon, MYB33 is responsive to sucrose and promotes the expression of SWEET11 and SWEET21, thereby facilitating sucrose transport from the cotyledon to the hypocotyl. Subsequently, sucrose transported from the cotyledon up-regulates the expression of GA2ox8c in the hypocotyl, which ultimately affects the length of the hypocotyl. During the domestication and improvement of soybean, an allele of MYB33 with enhanced abilities to promote SWEET11 and SWEET21 has gradually become enriched in landraces and cultivated varieties, SWEET11 and SWEET21 exhibit high conservation and have undergone a strong purified selection and GA2ox8c is under a strong artificial selection. Our findings identify a new molecular pathway in controlling soybean hypocotyl elongation and provide new insights into the molecular mechanism of sugar transport in soybean.

Types of Membrane Transporters and the Mechanisms of Interaction between Them and Reactive Oxygen Species in Plants.

Membrane transporters are proteins that mediate the entry and exit of substances through the plasma membrane and organellar membranes and are capable of recognizing and binding to specific substances, thereby facilitating substance transport. Membrane transporters are divided into different types, e.g., ion transporters, sugar transporters, amino acid transporters, and aquaporins, based on the substances they transport. These membrane transporters inhibit reactive oxygen species (ROS) generation through ion regulation, sugar and amino acid transport, hormone induction, and other mechanisms. They can also promote enzymatic and nonenzymatic reactions in plants, activate antioxidant enzyme activity, and promote ROS scavenging. Moreover, membrane transporters can transport plant growth regulators, solute proteins, redox potential regulators, and other substances involved in ROS metabolism through corresponding metabolic pathways, ultimately achieving ROS homeostasis in plants. In turn, ROS, as signaling molecules, can affect the activity of membrane transporters under abiotic stress through collaboration with ions and involvement in hormone metabolic pathways. The research described in this review provides a theoretical basis for improving plant stress resistance, promoting plant growth and development, and breeding high-quality plant varieties.

Research progress and application strategies of sugar transport mechanisms in rice.

In plants, carbohydrates are central products of photosynthesis. Rice is a staple that contributes to the daily calorie intake for over half of the world's population. Hence, the primary objective of rice cultivation is to maximize carbohydrate production. The "source-sink" theory is proposed as a valuable principle for guiding crop breeding. However, the "flow" research lag, especially in sugar transport, has hindered high-yield rice breeding progress. This review concentrates on the genetic and molecular foundations of sugar transport and its regulation, enhancing the fundamental understanding of sugar transport processes in plants. We illustrate that the apoplastic pathway is predominant over the symplastic pathway during phloem loading in rice. Sugar transport proteins, such as SUTs and SWEETs, are essential carriers for sugar transportation in the apoplastic pathway. Additionally, we have summarized a regulatory pathway for sugar transport genes in rice, highlighting the roles of transcription factors (OsDOF11, OsNF-YB1, OsNF-YC12, OsbZIP72, Nhd1), OsRRM (RNA Recognition Motif containing protein), and GFD1 (Grain Filling Duration 1). Recognizing that the research shortfall in this area stems from a lack of advanced research methods, we discuss cutting-edge analytical techniques such as Mass Spectrometry Imaging and single-cell RNA sequencing, which could provide profound insights into the dynamics of sugar distribution and the associated regulatory mechanisms. In summary, this comprehensive review serves as a valuable guide, directing researchers toward a deep understanding and future study of the intricate mechanisms governing sugar transport.

The SnRK2.3-AREB1-TST1/2 cascade activated by cytosolic glucose regulates sugar accumulation across tonoplasts in apple and tomato.

Soluble sugars are the core components of fruit quality, and the degree of sugar accumulation is largely determined by tonoplast-localized sugar transporters. We previously showed that two classes of tonoplast sugar transporters, MdERDL6 and MdTST1/2, coordinately regulate sugar accumulation in vacuoles. However, the mechanism underlying this coordination remains unknown. Here we discovered that two transcription factors, MdAREB1.1/1.2, regulate MdTST1/2 expression by binding their promoters in apple. The enhanced MdAREB1.1/1.2 expression in MdERDL6-1-overexpression plants resulted in an increase in MdTST1/2 expression and sugar concentration. Further studies established that MdSnRK2.3, whose expression could be regulated by expressing MdERDL6-1, could interact with and phosphorylate MdAREB1.1/1.2, thereby promoting the MdAREB1.1/1.2-mediated transcriptional activation of MdTST1/2. Finally, the orthologous SlAREB1.2 and SlSnRK2.3 exhibited similar functions in tomato fruit as in their apple counterparts. Together, our findings provide insights into the regulatory mechanism of tonoplast sugar transport exerted by SnRK2.3-AREB1-TST1/2 for fruit sugar accumulation.

Bioengineering of Canopy Photosynthesis in Rice for Securing Global Food Security: A Critical Review

The emerging threat of climate change is posing a scientific conundrum for global food and nutritional security. As a primary staple food, half of the global human population is supported by rice crop. Thus, enhancing rice yield is highly critical to ensure food security. Photosynthesis is the defining physiological process of plants that determines maximum attainable yield. Efficiently capturing solar radiation and converting the carbon assimilates into rice grain is critical to achieve high yield. Genetic interventions to modify the plant architecture for enhanced light capture can improve rice yield significantly. Enhancement of cellular photosynthesis by synthetic biology approaches targeting important nodes of the light harvesting and carbon assimilation pathways are critical for breaking yield ceiling. The possible targets for improving photosynthesis include the light capture, chloroplast electron transport, Calvin cycle enzymes, sugar transport mechanisms, minimization of photorespiration, and improving source–sink relations. Conversion of C3 rice into a C4 type plant is also an option being vigorously pursued. Here, we review the determinants of canopy photosynthesis in rice with special reference to genetic factors and cellular photosynthetic capacity.

Genome-Wide Identification and Expression Patterns of the SWEET Gene Family in Bletilla striata and its Responses to Low Temperature and Oxidative Stress.

SWEETs (sugars will eventually be exported transporters), a well-known class of sugar transporters, are involved in plant growth and development, sugar transport, biotic and abiotic stresses, etc. However, to date, there have been few investigations of SWEETs in Orchidaceae. In this study, 23 SWEET genes were identified in Bletilla striata for the first time, with an MtN3/saliva conserved domain, and were divided into four subgroups by phylogenetic tree. The same subfamily members had similar gene structures and motifs. Multiple cis-elements related to sugar and environmental stresses were found in the promoter region. Further, 21 genes were localized on 11 chromosomes and 2 paralogous pairs were found via intraspecific collinearity analysis. Expression profiling results showed that BsSWEETs were tissue-specific. It also revealed that BsSWEET10 and BsSWEET18 were responsive to low temperature and oxidative stresses. In addition, subcellular localization study indicated that BsSWEET15 and BsSWEET16 were localized in the cell membrane. This study provided important clues for the in-depth elucidation of the sugar transport mechanism of BsSWEET genes and their functional roles in response to abiotic stresses.

Comprehensive identification of sugar transporters in the Malus spp. genomes reveals their potential functions in sugar accumulation in apple fruits

• 130 sugar transporter genes were identified in the updated apple genome GDDH13 v1.1. • 57 ST genes were expressed in the cultivar Greensleeves, and 59 in the cultivar Fuji. • MdHT14.1 could transport glucose and fructose, while MdSUT2.1/2.2 and MdSWEET15.2 could transport sucrose. • Overexpression MdVGT1 or MdpGlcT2.1 in apple fruits significantly increased glucose, while overexpression of MdSUT2.1 increased sucrose or of MdSOT1 increased sorbitol. The transport of sugar across membranes is essential for maintaining cellular sugar homeostasis and metabolic balance in plant cells, but there is limited information about the sugar transporter family in economically important fleshy fruits. Here, 130 sugar transporter genes were identified in the updated apple genome (GDDH13 v1.1). The sugar transporter (ST) genes clustered into ten subfamilies. The apple ST genes mapped to all 17 apple chromosomes and had experienced whole-genome duplication (WGD)/segmental duplication and tandem duplication during the process of apple domestication. Expression profiles of the STs were analyzed in different tissues and during the stages of fruit development. In Malus × domestica , 57 ST genes were expressed in the cultivar ‘Greensleeves’, and 59 in ‘Fuji’. Different ST genes were highly expressed in mature leaves, shoot tips, young fruits, and mature fruits, indicating their divergent functions in different tissues. Heterologous expression experiments in yeast strains lacking STs indicated that MdHT14.1 is the sugar transporter with the highest affinity for glucose and fructose, while MdSUT2.1/2.2 and MdSWEET15.2 had the highest affinity for sucrose. Transient overexpression in apple fruits of MdVGT1 and MdpGlcT2.1 significantly increased glucose concentration, while overexpression of MdSUT2.1 increased sucrose level or of MdSOT1 increased sorbitol concentration. This study demonstrated the expansion and functional divergence of the sugar transporter gene family in domesticated apple and will enable further investigation of the molecular mechanisms of sugar transport and metabolism in apple and other important fleshy fruit crops.

Radial-axial transport coordination enhances sugar translocation in the phloem vasculature of plants.

Understanding mass transport of photosynthates in the phloem of plants is necessary for predicting plant carbon allocation, productivity, and responses to water and thermal stress. Several hypotheses about optimization of phloem structure and function and limitations of phloem transport under drought have been proposed and tested with models and anatomical data. However, the true impact of radial water exchange of phloem conduits with their surroundings on mass transport of photosynthates has not been addressed. Here, the physics of the Munch mechanism of sugar transport is re-evaluated to include local variations in viscosity resulting from the radial water exchange in two dimensions (axial and radial) using transient flow simulations. Model results show an increase in radial water exchange due to a decrease in sap viscosity leading to increased sugar front speed and axial mass transport across a wide range of phloem conduit lengths. This increase is around 40% for active loaders (e.g. crops) and around 20% for passive loaders (e.g. trees). Thus, sugar transport operates more efficiently than predicted by previous models that ignore these two effects. A faster front speed leads to higher phloem resiliency under drought because more sugar can be transported with a smaller pressure gradient.

Sugar transporters and their molecular tradeoffs during abiotic stress responses in plants.

Sugars as photosynthates are well known as energy providers and as building blocks of various structural components of plant cells, tissues and organs. Additionally, as a part of various sugar signaling pathways, they interact with other cellular machinery and influence many important cellular decisions in plants. Sugar signaling is further reliant on the differential distribution of sugars throughout the plant system. The distribution of sugars from source to sink tissues or within organelles of plant cells is a highly regulated process facilitated by various sugar transporters located in plasma membranes and organelle membranes, respectively. Sugar distribution, as well as signaling, is impacted during unfavorable environments such as extreme temperatures, salt, nutrient scarcity, or drought. Here, we have discussed the mechanism of sugar transport via various types of sugar transporters as well as their differential response during environmental stress exposure. The functional involvement of sugar transporters in plant's abiotic stress tolerance is also discussed. Besides, we have also highlighted the challenges in engineering sugar transporter proteins as well as the undeciphered modules associated with sugar transporters in plants. Thus, this review provides a comprehensive discussion on the role and regulation of sugar transporters during abiotic stresses and enables us to target the candidate sugar transporter(s) for crop improvement to develop climate-resilient crops.

When SWEETs Turn Tweens: Updates and Perspectives.

Sugar translocation between cells and between subcellular compartments in plants requires either plasmodesmata or a diverse array of sugar transporters. Interactions between plants and associated microorganisms also depend on sugar transporters. The sugars will eventually be exported transporter (SWEET) family is made up of conserved and essential transporters involved in many critical biological processes. The functional significance and small size of these proteins have motivated crystallographers to successfully capture several structures of SWEETs and their bacterial homologs in different conformations. These studies together with molecular dynamics simulations have provided unprecedented insights into sugar transport mechanisms in general and into substrate recognition of glucose and sucrose in particular. This review summarizes our current understanding of the SWEET family, from the atomic to the whole-plant level. We cover methods used for their characterization, theories about their evolutionary origins, biochemical properties, physiological functions, and regulation. We also include perspectives on the future work needed to translate basic research into higher crop yields.

Molecular mechanism of sugar transport in plants unveiled by structures of glucose/H+ symporter STP10.

Sugars are essential sources of energy and carbon and also function as key signalling molecules in plants. Sugar transport proteins (STP) are proton-coupled symporters responsible for uptake of glucose from the apoplast into plant cells. They are integral to organ development in symplastically isolated tissues such as seed, pollen and fruit. Additionally, STPs play a vital role in plant responses to stressors such as dehydration and prevalent fungal infections like rust and mildew. Here we present a structure of Arabidopsis thaliana STP10 in the inward-open conformation at 2.6 Å resolution and a structure of the outward-occluded conformation at improved 1.8 Å resolution, both with glucose and protons bound. The two structures describe key states in the STP transport cycle. Together with molecular dynamics simulations that establish protonation states and biochemical analysis, they pinpoint structural elements, conserved in all STPs, that clarify the basis of proton-to-glucose coupling. These results advance our understanding of monosaccharide uptake, which is essential for plant organ development, and set the stage for bioengineering strategies in crops.

The Hexose efflux from the peeled grape berry

Aim: The transport of sugars into grape berry mesocarp cells across the plasma and vacuolar membranes after onset of ripening is a complex process. Elements of the sugar transport mechanism may be assessed by exposing the mesocarp cells and investigating sugar movement across the membranes. The purpose of this study was to gain insights into the nature of the transport mechanism by creating conditions conducive to hexose efflux from the peeled berry.Methods and results: The experimental technique employed was a derivate of the ‘berry-cup’ technique. The skin of ripening cv. Shiraz berries was peeled in situ and, after an initial wash, hexose efflux into a collection medium (MES buffer) was monitored. Additionally, during the period of intensive sugar accumulation (one week after veraison) and two weeks later, hexose efflux was assessed following three modifications: (i) using berries excised from the vine, (ii) using MES buffer (2-(N-morpholino)ethanesulfonic acid, pH 5.5) containing PCMBS (p-chloromercuribenzenesulfonic acid, 1mM), and (iii) using cold (10°C) or warm (40°C) MES buffer. Hexose quantities collected into the buffer were dependent on ripening stage and buffer temperature, but they were not dependent on an intact berry-to-cluster connection. The inhibitory effect of PCMBS was observed early in ripening, but not two weeks later.Conclusions: These results lead us to the conclusion that the origin of the collected hexoses was vacuolar as opposed to vascular, and that the hexose efflux mechanism is differently sensitive to PCMBS at the two stages of ripening.Significance and impact of the study: This simple technique was effective at providing insights into hexose transport within the grape berry at the cellular level.

Molecular genetic mechanisms of sugar transport in plants in the absence and during arbuscular mycoryza development

The review is aimed to analyze molecular mechanisms of carbohydrate transport during the formation of arbuscular mycorrhiza (AM), a widespread symbiosis of plants with Glomeromycotina subdivision fungi. Due to AM-symbiosis, plants receive microelements, mainly phosphorus, and fungi are supplied by products of carbon assimilation. The study of sugar transport mechanisms in plants as well as between plants and symbiont is methodologically difficult because of the obligatory status of AM fungi. The mechanisms of carbohydrate transport in leaf and root cells are concerned, particular interest is paid to transporters, specific to AM structures. Several resumptive schemes are designed. SWEET family of transporters (Sugars Will Eventually be Exported Transporters), including AM-specific uniporters are reviewed. We summarize results on expression of genes encoding transporter in cells of plants without AM, in AM-plant cells with arbuscules and AM-plant cells without arbuscules. The data on genes of MST proteins family (Monosaccharide Transporters) participating in direct transport of sugars from the soil to the foliar mycelium of AM fungi are considered.

Natural genetic variation for expression of a SWEET transporter among wild species of Solanum lycopersicum (tomato) determines the hexose composition of ripening tomato fruit.

The sugar content of Solanum lycopersicum (tomato) fruit is a primary determinant of taste and quality. Cultivated tomato fruit are characterized by near-equimolar levels of the hexoses glucose and fructose, derived from the hydrolysis of translocated sucrose. As fructose is perceived as approximately twice as sweet as glucose, increasing its concentration at the expense of glucose can improve tomato fruit taste. Introgressions of the FgrH allele from the wild species Solanum habrochaites (LA1777) into cultivated tomato increased the fructose-to-glucose ratio of the ripe fruit by reducing glucose levels and concomitantly increasing fructose levels. In order to identify the function of the Fgr gene, we combined a fine-mapping strategy with RNAseq differential expression analysis of near-isogenic tomato lines. The results indicated that a SWEET protein was strongly upregulated in the lines with a high fructose-to-glucose ratio. Overexpressing the SWEET protein in transgenic tomato plants dramatically reduced the glucose levels and increased the fructose:glucose ratio in the developing fruit, thereby proving the function of the protein. The SWEET protein was localized to the plasma membrane and expression of the SlFgr gene in a yeast line lacking native hexose transporters complemented growth with glucose, but not with fructose. These results indicate that the SlFgr gene encodes a plasma membrane-localized glucose efflux transporter of the SWEET family, the overexpression of which reduces glucose levels and may allow for increased fructose levels. This article identifies the function of the tomato Fgr gene as a SWEET transporter, the upregulation of which leads to a modified sugar accumulation pattern in the fleshy fruit. The results point to the potential of the inedible wild species to improve fruit sugar accumulation via sugar transport mechanisms.

Molecular Mechanism of Sugar Transport by a SWEET Transporter

SWEET sugar transporters play critical roles in many physiological processes in plants and animals. They also serve as excellent models for understanding the alternating access transport mechanism. We captured the high-resolution structures of a SWEET family of sugar transporter in three major conformational states, including outward-open, occluded and inward-open conformations by protein engineering and crystallography. Our structure of a glucose bound form provided insights into substrate recognition. Furthermore, through unbiased molecular dynamics simulations, we observed spontaneous transitions from an outward-open to an inward-open state, as well as the accompanying substrate translocation events across the membrane. The unguided computational simulations matched well with the experimental structures. These data, along with functional studies and dynamic characterizations, suggest mechanisms to explain allosteric coupling of gates and transitions between conformational states. These studies lead to atomic level insights into how sugar is translocated across the membrane through an alternating access transporter.

Conformational Landscape of Substrate Specificity in the Fructose Transporter GLUT5 Determined via MBAR Molecular Dynamics

GLUT5 is a member of the glucose transporter (GLUT) family and channels fructose but not glucose through lipid membranes. Recent crystallographic data indicated that GLUT5 may possess a unique transport mechanism from other GLUT members; however, the details of this mechanism are unclear. 32μs equilibrium dynamics in combination with restrained MD were used to generate a conformational landscape of the sugar transport mechanism in four independent systems containing α-fructose, β-fructose, α-glucose, or β-glucose. A PMF was generated for each substrate using the MBAR method. The calculated PMF revealed two energy basins which were relatively consistent across the four sugars in this work. The first basin, and consequently the succeeding energy barrier, occurred at the flexible segment of the TM7 helix at the extracellular entrance of GLUT5. This flexible region was unresolved in recent GLUT5 crystal structures, highlighting its inherent flexibility. Here for the first time, we report a conformational landscape of GLUT5 and details of the required interactions of the TM7 loop with substrate. We demonstrated that initial entrance into the GLUT5 channel required overcoming an energy barrier associated with this loop. The second basin occurred in the GLUT5 central binding pocket, where the pivotal Q166 residue that is responsible for fructose specificity, made initial contact with incoming substrate. The barrier at this location was significantly higher for glucose compared to fructose. Moreover, we observed several other regions in the channel which showed specific favorable interactions with fructose. Such interactions could not occur with glucose substrates due to their minute but important steric and electrostatic incompatibilities with GLUT5. This work improved our understanding of the GLUT5 transport mechanism that is important for future development of therapies targeting sugar metabolism.

A Mass-Spectrometry Based Methodology to Unravel the Molecular Mechanisms of Sugar Transport

A Mass-Spectrometry Based Methodology to Unravel the Molecular Mechanisms of Sugar Transport

Dynamic Studies of Sweet Family Sugar Transporters through NMR Spectroscopy

Sugar is a primary carbon source for prokaryotes, plants, and humans. Recently, a new family of sugar transporters called SWEETs was discovered and found to transport a variety of mono- and disaccharides across the cell membrane. These proteins exist in all eukaryotic kingdoms including plants, fungi, and animals. SWEETs have ubiquitous expression throughout human cell lines and have been proposed to help mediate vesicular glucose efflux from intestine and liver cells. Mutations in sugar transporters lead to a variety of diseases related to homeostatic imbalance of sugars. Therefore, elucidating the sugar transport mechanism of this family of proteins is essential for developing therapeutic drugs for treatment of diseases related to the homeostatic imbalance of sugars. To date, the transport mechanism has been challenging to study due to the relatively weak binding affinity and difficulties associated with capturing a substrate bound structure of SWEET transporters. To provide atomic scale insight under functional conditions, a combination of solid-state and solution nuclear magnetic resonance (NMR) spectroscopy was used to probe conformational dynamics of this family of transporters upon substrate binding. Solid-state NMR experiments in native E. coli lipid bilayers were utilized to study the interactions between sugar substrates and the binding pocket of SWEETs. In addition, solution NMR in native-like lipid nanodiscs were used for analyzing conformational dynamics in this family of membrane proteins. The site-specific resolution available from NMR provided insights into protein dynamics, the nature of protein-substrate specificity, and the transport mechanism of the SWEET family.

Relationship between the morphological structure of floral nectaries and the formation, transport, and secretion of nectar in lychee

Key message The sugar in nectar secreted from the floral nectaries of lychee (Litchi chinensisSonn.) was composed of both the phloem sap and the starch synthesized by the nectariferous tissue itself. Sugar hydrolyzed from the starch and from the phloem might be transported to the endoplasmic reticulum (ER) and the Golgi cisternae, further transported via ER and Golgi vesicles, and eventually released to the spaces between the plasmalemma and cell wall by exocytosis. There was a specific sugar transport and secretory mechanism in the lychee floral nectary.