Update on SLC6A14 in lung and gastrointestinal physiology and physiopathology: focus on cystic fibrosis

Ruffin, Manon; Mercier, J.; Calmel, Claire; Mésinèle, Julie; Bigot, J. M.; Sutanto, Erika N.; Kicic, Anthony; Corvol, Harriet

doi:10.1007/s00018-020-03487-x

Cited by 22 publications

(27 citation statements)

References 78 publications

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“…Another study correlated SNPs in SLC6A14 gene with susceptibility to male infertility/subfertility in Macedonian/and Slovenian populations (Noveski et al, 2014), a phenomenon proposed to depend as well on availability of Trp and serotonin, associated with testosterone synthesis (Tinajero et al, 1993). SLC6A14 has been also proposed (Ruffin et al, 2020) to modify the phenotype of cystic fibrosis (CF) -a fatal genetic disorder caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene (Riordan et al, 1989;Rommens et al, 1989). Genome-wide analysis of CF patients from France and North America associated SNPs in SLC6A14 and SLC26A9 genes (Sun et al, 2012), the latter one coding the Cl −/ CO 3 2− exchanger.…”

Section: Physiological Consequences Of Slc6a14 Malfunctionmentioning

confidence: 99%

Amino Acid Transporter SLC6A14 (ATB0,+) – A Target in Combined Anti-cancer Therapy

Nałęcz

2020

Front. Cell Dev. Biol.

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Cancer cells are characterized by quick growth and proliferation, demanding constant supply of various nutrients. Several plasma membrane transporters delivering such compounds are upregulated in cancer. Solute carrier family 6 member 14 (SLC6A14), known as amino acid transporter B 0,+ (ATB 0,+) transports all amino acids with exception of the acidic ones: aspartate and glutamate. Its malfunctioning is correlated with several pathological states and it is upregulated in solid tumors. The high expression of SLC6A14 is prognostic and unfavorable in pancreatic cancer, while in breast cancer it is expressed in estrogen receptor positive cells. As many plasma membrane transporters it resides in endoplasmic reticulum (ER) membrane after translation before further trafficking through Golgi to the cell surface. Transporter exit from ER is strictly controlled. The proper folding of SLC6A14 was shown to be controlled from the cytoplasmic side by heat shock proteins, further exit from ER and formation of coatomer II (COPII) coated vesicles depends on specific interaction with COPII cargo-recognizing subunit SEC24C, phosphorylated by kinase AKT. Inhibition of heat shock proteins, known to be upregulated in cancer, directs SLC6A14 to degradation. Targeting proteins regulating SLC6A14 trafficking is proposed as an additional pharmacological treatment of cancer.

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Section: Physiological Consequences Of Slc6a14 Malfunctionmentioning

confidence: 99%

Amino Acid Transporter SLC6A14 (ATB0,+) – A Target in Combined Anti-cancer Therapy

Nałęcz

2020

Front. Cell Dev. Biol.

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“…These inhibitory concentrations are well above the physiological range. A follow up study using double-transfected MDCK-OATP4C1-p-gp cells simultaneously expressing basolaterally localized OATP4C1 and luminally localized export pump P-glycoprotein demonstrated vectorial transport of L-arginine, L-homoarginine, and ADMA suggesting, that also this ABC-transporter may be important for their renal homeostasis of these compounds [ 185 ].…”

Section: Transporter Families Shown To Transport L-arginine And/ormentioning

confidence: 99%

Transport of L-Arginine Related Cardiovascular Risk Markers

Banjarnahor

Rodionov

König

et al. 2020

JCM

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L-arginine and its derivatives, asymmetric and symmetric dimethylarginine (ADMA and SDMA) and L-homoarginine, have emerged as cardiovascular biomarkers linked to cardiovascular outcomes and various metabolic and functional pathways such as NO-mediated endothelial function. Cellular uptake and efflux of L-arginine and its derivatives are facilitated by transport proteins. In this respect the cationic amino acid transporters CAT1 and CAT2 (SLC7A1 and SLC7A2) and the system y+L amino acid transporters (SLC7A6 and SLC7A7) have been most extensively investigated, so far, but the number of transporters shown to mediate the transport of L-arginine and its derivatives is constantly increasing. In the present review we assess the growing body of evidence regarding the function, expression, and clinical relevance of these transporters and their possible relation to cardiovascular diseases.

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“…In the last decade, the over-expression of ATB 0,+ in several human cancers became a hallmark of this pathology similar to what it is described for other plasma membrane transporters (Bhutia and Ganapathy, 2016 and Table 1). This has been linked particularly with the ability of ATB 0,+ to mediate high capacity transport of amino acids (Gupta et al, 2006;Ruffin et al, 2020) making this transporter a druggable target (Karunakaran et al, 2011). However, in light of its ability to mediate uptake of carnitine, it cannot be excluded that the over-expression of ATB 0,+ is also responsible for providing this essential co-factor to those cells in which FAO is responsible for deriving energy required for cell growth and progression.…”

Section: Implications Of Ct2 In Cancermentioning

confidence: 99%