The Na<sup>+</sup>‐coupled glucose transporter <scp>SGLT</scp>2 interacts with its accessory unit <scp>MAP</scp>17 <i>in vitro</i> and their expressions overlap in the renal proximal tubule

Calado, Joaquim; Santos, Ana Rita; Aires, Inês; Lebre, Firmina; Nolasco, Fernando; Rueff, José; Ramalho, José S.

doi:10.1002/1873-3468.13233

Cited by 8 publications

(4 citation statements)

References 22 publications

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“…MAP17 interacts indirectly with the cytoplasmic C-terminal domain of NaPi-IIa through a PDZ protein. However, there is no comparable C-terminal domain of SGLT2, but there is evidence that MAP17 may be a β -subunit of SGLT2 in the plasma membrane of the S1 and S2 segments (31,33).…”

Section: Sglt Biologymentioning

confidence: 99%

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SGLT2 Inhibitors: Physiology and Pharmacology

Wright¹

2021

Kidney360

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SGLTs are sodium glucose transporters found on the luminal membrane of the proximal tubule, where they reabsorb some 180 grams (one mole) of glucose from the glomerular filtrate each day. The natural glucoside phlorizin completely blocks glucose reabsorption. Oral SGLT2 inhibitors are rapidly absorbed into the blood stream where they remain in in the circulation for hours. On glomerular filtration, they bind specifically to SGLT2 in the luminal membrane of the early proximal tubule to reduce glucose reabsorption by 50-60%. Because of glucose excretion, these drugs lower plasma glucose and glycosylated hemoglobin levels in patients with type 2 diabetes mellitus. The drugs also protect against heart and renal failure. The aim of this review is to summarize what is currently known about the physiology of renal SGLTs and the pharmacology of SGLT drugs.

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Section: Sglt Biologymentioning

confidence: 99%

“…SGLT2 is robustly expressed in cultured mammalian cells at 37°C (34 –37), and there is no MAP17 in these cells (32,33). The kinetic properties of SGLT2 in cultured cells and oocytes are similar (35,38), and those for HEK293T cells are summarized in Table 1.…”

Section: Sglt Biologymentioning

confidence: 99%

SGLT2 Inhibitors: Physiology and Pharmacology

Wright¹

2021

Kidney360

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“…For example, the importance of interaction partners for transporter regulation has been already shown for the Na + -glucose cotransporter 2 (SGLT2) and for the Na + -dependent neutral amino acid transporter B (0)AT1 in the kidneys. Here, a direct interaction with PDZK1-interacting protein 1 (PDZK1P1, also known as MAP17, a protein mainly expressed in the apical brush border membranes from renal proximal tubules) stimulates SGLT2 activity (Calado et al, 2018), and the interaction of B(0) AT1 with collectrin stabilizes the transporter in the apical plasma membrane of renal proximal tubules (Camargo et al, 2009). Focusing on OCT1, a specific interaction of OCT1 with another protein, may explain why the transporter has a clear basolateral cellular localization in some tissues, while in others, it appears to be expressed on the apical membrane domain.…”

Section: Cellular Processing Of Octsmentioning

confidence: 99%

Regulation Mechanisms of Expression and Function of Organic Cation Transporter 1

Ciarimboli¹

2021

Front. Pharmacol.

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The organic cation transporter 1 (OCT1) belongs together with OCT2 and OCT3 to the solute carrier family 22 (SLC22). OCTs are involved in the movement of organic cations through the plasma membrane. In humans, OCT1 is mainly expressed in the sinusoidal membrane of hepatocytes, while in rodents, OCT1 is strongly represented also in the basolateral membrane of renal proximal tubule cells. Considering that organic cations of endogenous origin are important neurotransmitters and that those of exogenous origin are important drugs, these transporters have significant physiological and pharmacological implications. Because of the high expression of OCTs in excretory organs, their activity has the potential to significantly impact not only local but also systemic concentration of their substrates. Even though many aspects governing OCT function, interaction with substrates, and pharmacological role have been extensively investigated, less is known about regulation of OCTs. Possible mechanisms of regulation include genetic and epigenetic modifications, rapid regulation processes induced by kinases, regulation caused by protein–protein interaction, and long-term regulation induced by specific metabolic and pathological situations. In this mini-review, the known regulatory processes of OCT1 expression and function obtained from in vitro and in vivo studies are summarized. Further research should be addressed to integrate this knowledge to known aspects of OCT1 physiology and pharmacology.

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“…First isolated based on its overexpression in epithelial cancers relative to normal tissue, PDZK1IP1 (also known as DD96 and MAP17) encodes a 17 kDa transmembrane protein that interacts with the protein PDZK1, which contains four PDZ domains (Kocher et al, 1995;Kocher et al, 1996). PDZK1IP1 stimulates the sodium dependent uptake of mannose and glucose through the regulation of sodium-glucose linked transporter (SGLT) family and bypasses TNF-a dependent growth arrest (Blasco et al, 2003;Calado et al, 2018;Coady et al, 2017;Guijarro et al, 2007a;Kocher et al, 1998;Perez et al, 2013). PDZK1IP1 is reported to have contradictory effects on cell growth in culture and tumor growth in nude mice.…”

Section: Introductionmentioning

confidence: 99%

A local tumor microenvironment acquired super-enhancer induces an oncogenic driver for efficient growth under oxidative conditions in colorectal carcinoma

Zhou

Martin

et al. 2021

Preprint

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Tumors exhibit widespread enhancer landscape reprogramming compared to normal tissue. The etiology is believed to be largely cell-intrinsic in non-hormonal cancers, attributed to such genomic alterations as focal amplification of non-coding regions, aberrant activation of transcription factors, and non-coding mutations creating de novo transcription factor binding sites. Here, using freshly resected primary CRC tumors and patient-matched adjacent normal colon epithelia, we find divergent epigenetic landscapes between primary CRC tumors and CRC cell lines. We identify a unique super-enhancer signature largely absent in cell culture. Intriguingly, this phenomenon extends to highly recurrent aberrant super-enhancers gained in CRC over patient-matched normal epithelium suggesting novel insight into the etiology of enhancer reprogramming in CRC and its downstream relevance to tumor biology. We find one such super-enhancer activated in epithelial cancer cells due to surrounding inflammation in the tumor microenvironment. We restore this super-enhancer and its expressed gene, PDZK1IP1, following treatment with cytokines or xenotransplantation into nude mice, thus demonstrating its etiology via local tumor microenvironment acquisition. Building on its known role in glucose uptake via SGLT receptors, we demonstrate mechanistically that PDZK1IP1 enhances the reductive capacity CRC cancer cells via the pentose phosphate pathway using polar metabolomic profiling. We show this activation enables efficient growth under oxidative conditions both in vitro and in vivo, challenging the previous notion that PDZK1IP1 acts as a tumor suppressor in CRC. Collectively, these observations highlight the biologic significance of epigenomic profiling on patient-matched primary specimens and identify this microenvironment-acquired super-enhancer as an oncogenic driver in the setting of the inflamed tumor.

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The Na⁺‐coupled glucose transporter SGLT2 interacts with its accessory unit MAP17 in vitro and their expressions overlap in the renal proximal tubule

Cited by 8 publications

References 22 publications

SGLT2 Inhibitors: Physiology and Pharmacology

SGLT2 Inhibitors: Physiology and Pharmacology

Regulation Mechanisms of Expression and Function of Organic Cation Transporter 1

A local tumor microenvironment acquired super-enhancer induces an oncogenic driver for efficient growth under oxidative conditions in colorectal carcinoma

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The Na+‐coupled glucose transporter SGLT2 interacts with its accessory unit MAP17 in vitro and their expressions overlap in the renal proximal tubule

Cited by 8 publications

References 22 publications

SGLT2 Inhibitors: Physiology and Pharmacology

SGLT2 Inhibitors: Physiology and Pharmacology

Regulation Mechanisms of Expression and Function of Organic Cation Transporter 1

A local tumor microenvironment acquired super-enhancer induces an oncogenic driver for efficient growth under oxidative conditions in colorectal carcinoma

Contact Info

Product

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The Na⁺‐coupled glucose transporter SGLT2 interacts with its accessory unit MAP17 in vitro and their expressions overlap in the renal proximal tubule