Novel Mutation in SLC6A19 Causing Late-Onset Seizures in Hartnup Disorder

Cheon, Chong Kun; Lee, Beom Hee; Ko, Jung Min; Kim, Hyun Ji

doi:10.1016/j.pediatrneurol.2010.01.009

Cited by 37 publications

(13 citation statements)

References 10 publications

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“…Twenty-one additional mutations were further described to cause the disease, including deletions, missense, nonsense and splice site mutations on the gene SLC6A19, as depicted in Figure 4. [90][91][92][93] Most of the patients are compound heterozygous, which could partially contribute to the variable symptoms observed in patients ( Table 2). …”

Section: 11mentioning

confidence: 99%

Collectrin and ACE2 in renal and intestinal amino acid transport

Singer¹,

Camargo²

2011

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Neutral amino acid transporters of the SLC6 family are expressed at the apical membrane of kidney and/or small intestine, where they (re-)absorb amino acids into the body. In this review we present the results concerning the dependence of their apical expression on their association to partner proteins. We will in particular focus on the situation of B(0)AT1 and B(0)AT3, which associate with members of the renin-angiotensin system (RAS), namely Tmem27 and angiotensin-converting enzyme 2 (ACE2), in a tissue specific manner. The role of this association in relation to the formation of a functional unit related to Na(+) or amino acid transport will be assessed. We will conclude with some remarks concerning the relevance of this association to Hartnup disorder, where some mutations have been shown to differentially interact with the partner proteins

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Section: 11mentioning

confidence: 99%

Collectrin and ACE2 in renal and intestinal amino acid transport

Singer¹,

Camargo²

2011

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“…Loss of function mutations of SLC6A19 lead to Hartnup disease, a classical autosomal recessive disorder with aminoaciduria resulting in several clinical symptoms such as photo-sensitive skinrash, cerebellar ataxia, pellagra, dementia and late-onset seizures [3,[5][6][7]. SLC6A19 is under powerful regulation by the angiotensin-converting enzyme 2 (ACE2) and collectrin [3].…”

Section: Introductionmentioning

confidence: 99%

Up-Regulation of Amino Acid Transporter SLC6A19 Activity and Surface Protein Abundance by PKB/Akt and PIKfyve

Bogatikov

Muñoz

Pakladok

et al. 2012

Cell Physiol Biochem

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Background: The amino acid transporter B0AT1 (SLC6A19) accomplishes concentrative cellular uptake of neutral amino acids. SLC6A19 is stimulated by serum- & glucocorticoid-inducible kinase (SGK) isoforms. SGKs are related to PKB/Akt isoforms, which also stimulate several amino acid transporters. PKB/Akt modulates glucose transport in part by phosphorylating and thus activating phosphatidylinositol-3-phosphate-5-kinase (PIKfyve), which fosters carrier protein insertion into the cell membrane. The present study explored whether PKB/Akt and/or PIKfyve stimulate SLC6A19. Methods: SLC6A19 was expressed in Xenopus oocytes with or without wild-type PKB/Akt or inactive ^T308A/S473APKB/Akt without or with additional expression of wild-type PIKfyve or PKB/Akt-resistant ^S318APIKfyve. Electrogenic amino acid transport was determined by dual electrode voltage clamping. Results: In SLC6A19-expressing oocytes but not in water-injected oocytes, the addition of the neutral amino acid L-leucine (2 mM) to the bath generated a current (I_le), which was significantly increased following coexpression of PKB/Akt, but not by coexpression of ^T308A/S473APKB/Akt. The effect of PKB/Akt was augmented by additional coexpression of PIKfyve but not of ^S318APIKfyve. Coexpression of PKB/Akt enhanced the maximal transport rate without significantly modifying the affinity of the carrier. The decline of I_le following inhibition of carrier insertion by brefeldin A (5 µM) was similar in the absence and presence of PKB/Akt indicating that PKB/Akt stimulated carrier insertion into rather than inhibiting carrier retrieval from the cell membrane. Conclusion: PKB/Akt up-regulates SLC6A19 activity, which may foster amino acid uptake into PKB/Akt-expressing epithelial and tumor cells.

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“…ATP1A2 encodes the α2 isoform of the Na + ,K + -ATPase's catalytic subunit, an ion channel/ion transporter. SLC6A19 encodes the amino acid transporter B(0)AT1, mediating neutral amino acid transport from the luminal compartment to the intracellular space [29]. In generally, MT1M, ATP1A2, SLC6A19 and TRPV6 relates to mineral absorption.…”

Section: Effect Of the Mineral Absorption Related Genes From Gecko Scmentioning

confidence: 99%

CRISPR/Cas9-Mediated Whole Genomic Wide Knockout Screening Identifies Specific Genes Related to Mineral Absorption Involving in PM2.5 Liver Toxicity

Peng¹,

Yi²,

Wang³

et al. 2020

Preprint

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Background: PM2.5 , also known as fine particles, refers to particulate matter with a dynamic diameter of ≦ 2.5 µm in air pollutants, carrying toxic substances (e.g. heavy metals or minerals), which can pass through the alveolar epithelium and enter the bloodstream and tissues, can have more serious health problems, such as non-alcoholic fatty liver and hepatocellular carcinoma. However, the underlying mechanisms for toxic effect of PM2.5 are poorly understood. Results: Here, we subjected L02 cells to expose of PM2.5 and performed a pooled genome‐wide CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) loss of function screen to discover new potential targets for PM2.5. Enrichr and KEGG were employed to identify candidate genes which might involve in PM2.5 toxicity. We found that ATP1A2(ATPase Na+/K+ transporting subunit alpha 2), MT1M(metallothionein 1M), SLC6A19(solute carrier family 6 member 19) and TRPV6(transient receptor potential cation channel subfamily V member 6) genes contributed to PM2.5 toxicity involving in mineral absorption pathway. Moreover, we demonstrated that these candidate genes deficiency increased the cell viability and attenuated apoptosis in cells explored to PM2.5. Conclusions: ATP1A2, MT1M, SLC6A19 and TRPV6 contribute to PM2.5 toxicity and may be potential therapeutic targets for PM2.5 related diseases.

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Novel Mutation in SLC6A19 Causing Late-Onset Seizures in Hartnup Disorder

Cited by 37 publications

References 10 publications

Collectrin and ACE2 in renal and intestinal amino acid transport

Collectrin and ACE2 in renal and intestinal amino acid transport

Up-Regulation of Amino Acid Transporter SLC6A19 Activity and Surface Protein Abundance by PKB/Akt and PIKfyve

CRISPR/Cas9-Mediated Whole Genomic Wide Knockout Screening Identifies Specific Genes Related to Mineral Absorption Involving in PM2.5 Liver Toxicity

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