scholarly journals Novel and Unexpected Functions of SGLTs

Physiology ◽  
2017 ◽  
Vol 32 (6) ◽  
pp. 435-443 ◽  
Author(s):  
Ernest M. Wright ◽  
Chiara Ghezzi ◽  
Donald D. F. Loo
Keyword(s):  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Glucose Sensor ◽  
Human Gene ◽  
Gene Families ◽  
Major Facilitator Superfamily ◽  
Sodium Glucose Cotransporter ◽  
Major Facilitator ◽  
Familial Renal Glucosuria ◽  
Opening And Closing

It has been 30 years since the intestinal sodium glucose cotransporter SGLT1 was cloned, and, in the intervening years, there have been many advances that have influenced physiology and medicine. Among the first was that SGLT1 is the founding member of the human gene family SLC5, containing 11 diverse transporters and a glucose sensor. Equally surprising was that SGLTs are members of a structural family of cotransporters and exchangers in different gene families. This led to the conclusion that these proteins operate by a mechanism where transport involves the opening and closing of external and internal gates. The mechanism is shared by a wide variety of transporters in different structural families, e.g., the human facilitated glucose transporters (SLC2) in the huge major facilitator superfamily (MFS). Not surprising is the finding that mutations in Sglt genes cause the rare diseases glucose-galactose-malabsorption (GGM) and familial renal glucosuria (FRG). However, it was not envisaged that SGLT inhibitors would be used to treat diabetes mellitus, and these drugs may be able to treat cancer. Finally, in 2017, we have just learned that SGLT1 may be required to resist infection and to avoid recurrent pregnancy loss.

scholarly journals Genome-wide identification and analyses of tomato (Solanum lycopersicum L.) high-affinity nitrate transporter 2 (NRT2) family genes and their responses to drought and salinity

2021 ◽  
Author(s):  
M. AYDIN AKBUDAK ◽  
Ertugrul Filiz ◽  
Durmus Cetin
Keyword(s):  
Solanum Lycopersicum ◽  
Expression Profiles ◽  
Gene Families ◽  
Major Facilitator Superfamily ◽  
Nitrate Transporter ◽  
Tomato Genome ◽  
High Affinity ◽  
Solanum Lycopersicum L ◽  
Major Facilitator ◽  
Systematic Identification

High-affinity nitrate transporter 2 (NRT2) proteins have vital roles in nitrate (NO3-) uptake and translocation in plants. The gene families coding NRT2 proteins have been identified and functionally characterized in many plant species. However, no systematic identification of NRT2 family members have been reported in tomato (Solanum lycopersicum). There is also little known about their expression profiles under environmental stresses. Accordingly, the present study aimed to identify NRT2 gene family in the tomato genome; then, investigate them in detail through bioinformatics, physiological and expression analyses. As a result, four novel NRT2 genes were identified in the tomato genome, all of which contain the same domain belonging to the Major Facilitator Superfamily (PF07690). The co-expression network of SlNRT genes revealed that they were co-expressed with several other genes in many different molecular pathways including transport, photosynthesis, fatty acid metabolism and amino acid catabolism. Programming many crucial physiological and metabolic pathways, various numbers of phosphorylation sites were predicted in the NRT2 proteins.

Thyroid peroxidase antibodies do not predict outcome in 900 women with recurrent pregnancy loss

2017 ◽  
Author(s):  
Sofie Bliddal ◽  
Nielsen Henriette Svarre ◽  
Aase Krogh-Rasmussen ◽  
Kolte Astrid Marie ◽  
Christiansen Ole Bjarne ◽  
...  
Keyword(s):  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Thyroid Peroxidase ◽  
Thyroid Peroxidase Antibodies

Prophylactic Measures in Early Recurrent Pregnancy Loss in Women with Polycystic Ovary Syndrome and Hyperhomocysteinemia

2019 ◽  
Vol 87 (March) ◽  
pp. 195-199
Author(s):  
MAHMOUD F. MAHDIA, M.Sc. TAREK M. EL-HAWARY, M.D. ◽  
SHAHENAZ H. EL-SHORBAGY, M.D. NAREMAAN M. EL-HAMAMY, M.D.
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Prophylactic Measures

scholarly journals Untargeted Metabolomics Uncovers the Essential Lysine Transporter in Toxoplasma gondii

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 476
Author(s):  
Joachim Kloehn ◽  
Matteo Lunghi ◽  
Emmanuel Varesio ◽  
David Dubois ◽  
Dominique Soldati-Favre
Keyword(s):  
Amino Acids ◽  
Toxoplasma Gondii ◽  
Rna Degradation ◽  
Major Facilitator Superfamily ◽  
Untargeted Metabolomics ◽  
Apicomplexan Parasites ◽  
Obligate Intracellular ◽  
Intracellular Parasites ◽  
Major Facilitator ◽  
Plasma Membrane Transporter

Apicomplexan parasites are responsible for devastating diseases, including malaria, toxoplasmosis, and cryptosporidiosis. Current treatments are limited by emerging resistance to, as well as the high cost and toxicity of existing drugs. As obligate intracellular parasites, apicomplexans rely on the uptake of many essential metabolites from their host. Toxoplasma gondii, the causative agent of toxoplasmosis, is auxotrophic for several metabolites, including sugars (e.g., myo-inositol), amino acids (e.g., tyrosine), lipidic compounds and lipid precursors (cholesterol, choline), vitamins, cofactors (thiamine) and others. To date, only few apicomplexan metabolite transporters have been characterized and assigned a substrate. Here, we set out to investigate whether untargeted metabolomics can be used to identify the substrate of an uncharacterized transporter. Based on existing genome- and proteome-wide datasets, we have identified an essential plasma membrane transporter of the major facilitator superfamily in T. gondii—previously termed TgApiAT6-1. Using an inducible system based on RNA degradation, TgApiAT6-1 was depleted, and the mutant parasite’s metabolome was compared to that of non-depleted parasites. The most significantly reduced metabolite in parasites depleted in TgApiAT6-1 was identified as the amino acid lysine, for which T. gondii is predicted to be auxotrophic. Using stable isotope-labeled amino acids, we confirmed that TgApiAT6-1 is required for efficient lysine uptake. Our findings highlight untargeted metabolomics as a powerful tool to identify the substrate of orphan transporters.

scholarly journals Structural basis of inhibition of a transporter from Staphylococcus aureus, NorC, through a single-domain camelid antibody

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Sushant Kumar ◽  
Arunabh Athreya ◽  
Ashutosh Gulati ◽  
Rahul Mony Nair ◽  
Ithayaraja Mahendran ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Pathogenic Bacteria ◽  
Major Facilitator Superfamily ◽  
Single Domain ◽  
Fluoroquinolone Resistance ◽  
Structural Basis ◽  
Antibody Complex ◽  
Complementarity Determining Regions ◽  
Major Facilitator ◽  
Alternating Access

AbstractTransporters play vital roles in acquiring antimicrobial resistance among pathogenic bacteria. In this study, we report the X-ray structure of NorC, a 14-transmembrane major facilitator superfamily member that is implicated in fluoroquinolone resistance in drug-resistant Staphylococcus aureus strains, at a resolution of 3.6 Å. The NorC structure was determined in complex with a single-domain camelid antibody that interacts at the extracellular face of the transporter and stabilizes it in an outward-open conformation. The complementarity determining regions of the antibody enter and block solvent access to the interior of the vestibule, thereby inhibiting alternating-access. NorC specifically interacts with an organic cation, tetraphenylphosphonium, although it does not demonstrate an ability to transport it. The interaction is compromised in the presence of NorC-antibody complex, consequently establishing a strategy to detect and block NorC and related transporters through the use of single-domain camelid antibodies.

Differentially expressed circulating microRNAs associated with idiopathic recurrent pregnancy loss

Gene ◽  
2021 ◽  
Vol 768 ◽  
pp. 145334
Author(s):  
Deeba S. Jairajpuri ◽  
Zainab H. Malalla ◽  
Naeema Mahmood ◽  
Farah Khan ◽  
Wassim Y. Almawi
Keyword(s):  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Differentially Expressed ◽  
Circulating Micrornas
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