Long evolutionary conservation and considerable tissue specificity of several atypical solute carrier transporters

Sreedharan, Smitha; Stephansson, Olga; Schiöth, Helgi B.; Fredriksson, Robert

doi:10.1016/j.gene.2010.10.011

Cited by 54 publications

(59 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4A). This is consistent with findings in other bilateral species (18). Marginal mRNA levels could be detected in trachea, kidney, prostate, salivary gland, testis, and whole skin, whereas no SLC7A14 mRNA was detected in heart, fetal liver, placenta, thymus, and thyroid gland.…”

Section: Discussionsupporting

confidence: 92%

A Chimera Carrying the Functional Domain of the Orphan Protein SLC7A14 in the Backbone of SLC7A2 Mediates Trans-stimulated Arginine Transport

Jaenecke

Boissel

Lemke

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: The molecular identity of the lysosomal transporter for cationic amino acids, system c, remains unknown. Results: SLC7A14 is a lysosomal localized protein with a functional domain that mediates arginine transport. Conclusion: SLC7A14 may mediate cationic amino acid transport across lysosomal membranes. Significance: As system c represents a salvage pathway in the therapy of cystinosis, characterization of SLC7A14 might help to develop better drugs.

show abstract

Section: Discussionsupporting

confidence: 92%

A Chimera Carrying the Functional Domain of the Orphan Protein SLC7A14 in the Backbone of SLC7A2 Mediates Trans-stimulated Arginine Transport

Jaenecke

Boissel

Lemke

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…We also observed a positive correlations between liver iron concentration and hepatic Slc30a10 gene expression in the C57Bl6 mice (Foster et al, 2017). Our finding of decreased Slc30a10 expression in the liver is surprising and seems to run contrary to the predicted importance for this organ and transporter in Mn homeostasis (Quadri et al, 2012; Sreedharan et al, 2011). …”

Section: Discussioncontrasting

confidence: 99%

Neonatal C57BL/6J and parkin mice respond differently following developmental manganese exposure: Result of a high dose pilot study

et al. 2018

View full text Add to dashboard Cite

It has been suggested that childhood exposure to neurotoxicants may increase the risk of Parkinson’s disease (PD) or other neurodegenerative disease in adults. Some recessive forms of PD have been linked to loss-of-function mutations in the Park2 gene that encodes for parkin. The purpose of this pilot study was to evaluate whether responses to neonatal manganese (Mn) exposure differ in mice with a Park2 gene defect (parkin mice) when compared with a wildtype strain (C57BL/6J). Neonatal parkin and C57BL/6J littermates were randomly assigned to 0, 11, or 25 mg Mn/kg-day dose groups with oral exposures occurring from postnatal day (PND) 1 through PND 28. Motor activity was measured on PND 19–22 and 29–32. Tissue Mn concentrations were measured in liver, femur, olfactory bulb, frontal cortex, and striatum on PND 29. Hepatic and frontal cortex gene expression of Slc11a2, Slc40a1, Slc30a10, Hamp (liver only), and Park2 were also measured on PND 29. Some strain differences were seen. As expected, decreased hepatic and frontal cortex Park2 expression was seen in the parkin mice when compared with C57BL/6J mice. Untreated parkin mice also had higher liver and femur Mn concentrations when compared with the C57BL/6J mice. Exposure to > 11 mg Mn/kg-day was associated with increased brain Mn concentrations in all mice, no strain difference was observed. Manganese exposure in C57Bl6, but not parkin mice, was associated with a negative correlation between striatal Mn concentration and motor activity. Manganese exposure was not associated with changes in frontal cortex gene expression. Decreased hepatic Slc30a10, Slc40a1, and Hamp expression were seen in PND 29 C57BL/6J mice given 25 mg Mn/kg-day. In contrast, Mn exposure was only associated with decreased Hamp expression in the parkin mice. Our results suggest that the Parkin gene defect did not increase the susceptibility of neonatal mice to adverse health effects associated with high-dose Mn exposure.

show abstract

“…Based on sequence similarities, two orphan putative transporters MFSD14A and MFSD14B have previously been classified as atypical SLCs belonging to the major facilitator superfamily (MFS) Pfam clan (Sreedharan et al, 2011). The proteins were first named according to large cDNA sequencing projects as hippocampus abundant transcript 1, HIAT1, and hippocampus abundant transcript like 1, HIATL1 (Fredriksson et al, 2008) but was later on renamed to MFSD14A and MFSD14B.…”

Section: Introductionmentioning

confidence: 99%

“…The MFS is a diverse family, and despite shared similar functions, they share weak sequence similarities between members in conventional linear sequence alignment studies (Madej et al, 2013). MFS proteins are present in species from bacteria to eukaryotes (Lemieux, 2007), and both MFSD14A and MFSD14B are conserved in several, including mice and Drosophila melanogaster (Pao et al, 1998; Sreedharan et al, 2011). Mfsd14a encodes a protein of 490 amino acids, revealing similarities to sugar transporters due to the sugar transporter specific motif found between the second and third putative transmembrane domains (Gerhard et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Putative Membrane-Bound Transporters MFSD14A and MFSD14B Are Neuronal and Affected by Nutrient Availability

Lekholm

Perland

Eriksson

et al. 2017

Front. Mol. Neurosci.

Self Cite

View full text Add to dashboard Cite

Characterization of orphan transporters is of importance due to their involvement in cellular homeostasis but also in pharmacokinetics and pharmacodynamics. The tissue and cellular localization, as well as function, is still unknown for many of the solute carriers belonging to the major facilitator superfamily (MFS) Pfam clan. Here, we have characterized two putative novel transporters MFSD14A (HIAT1) and MFSD14B (HIATL1) in the mouse central nervous system and found protein staining throughout the adult mouse brain. Both transporters localized to neurons and MFSD14A co-localized with the Golgi marker Giantin in primary embryonic cortex cultures, while MFSD14B staining co-localized with an endoplasmic retention marker, KDEL. Based on phylogenetic clustering analyses, we predict both to have organic substrate profiles, and possible involvement in energy homeostasis. Therefore, we monitored gene regulation changes in mouse embryonic primary cultures after amino acid starvations and found both transporters to be upregulated after 3 h of starvation. Interestingly, in mice subjected to 24 h of food starvation, both transporters were downregulated in the hypothalamus, while Mfsd14a was also downregulated in the brainstem. In addition, in mice fed a high fat diet (HFD), upregulation of both transporters was seen in the striatum. Both MFSD14A and MFSD14B were intracellular neuronal membrane-bound proteins, expressed in the Golgi and Endoplasmic reticulum, affected by both starvation and HFD to varying degree in the mouse brain.

show abstract

Long evolutionary conservation and considerable tissue specificity of several atypical solute carrier transporters

Cited by 54 publications

References 27 publications

A Chimera Carrying the Functional Domain of the Orphan Protein SLC7A14 in the Backbone of SLC7A2 Mediates Trans-stimulated Arginine Transport

A Chimera Carrying the Functional Domain of the Orphan Protein SLC7A14 in the Backbone of SLC7A2 Mediates Trans-stimulated Arginine Transport

Neonatal C57BL/6J and parkin mice respond differently following developmental manganese exposure: Result of a high dose pilot study

Putative Membrane-Bound Transporters MFSD14A and MFSD14B Are Neuronal and Affected by Nutrient Availability

Contact Info

Product

Resources

About