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Structural predicti...
Structural prediction of two novel human atypical SLC transporters, MFSD4A and MFSD9, and their neuroanatomical distribution in mice
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- Perland, Emelie (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Funktionell farmakologi,Institutionen för farmaceutisk biovetenskap, Molecular Neuropharmacology
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- Hellsten, Sofie V (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Molecular Neuropharmacology
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- Schweizer, Nadine, 1985- (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Molecular Neuropharmacology
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- Arapi, Vasiliki (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Molecular Neuropharmacology
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- Rezayee, Fatemah (author)
- Karolinska Institutet,Uppsala universitet,Institutionen för neurovetenskap,Funktionell farmakologi
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- Bushra, Mona (author)
- Uppsala universitet,Institutionen för neurovetenskap,Funktionell farmakologi
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- Fredriksson, Robert (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Molekylär Neurofarmakologi
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(creator_code:org_t)
- 2017-10-19
- 2017
- English.
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:10
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Abstract
Subject headings
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- Out of the 430 known solute carriers (SLC) in humans, 30% are still orphan transporters regarding structure, distribution or function. Approximately one third of all SLCs belong to the evolutionary conserved and functionally diverse Major Facilitator Superfamily (MFS). Here, we studied the orphan proteins, MFSD4A and MFSD9, which are atypical SLCs of MFS type. Hidden Markov Models were used to identify orthologues in several vertebrates, and human MFSD4A and MFSD9 share high sequence identity with their identified orthologues. MFSD4A and MFSD9 also shared more than 20% sequence identity with other phylogenetically related SLC and MFSD proteins, allowing new family clustering. Homology models displayed 12 transmembrane segments for both proteins, which were predicted to fold into a transporter-shaped structure. Furthermore, we analysed the location of MFSD4A and MFSD9 in adult mouse brain using immunohistochemistry, showing abundant neuronal protein staining. As MFSD4A and MFSD9 are plausible transporters expressed in food regulatory brain areas, we monitored transcriptional changes in several mouse brain areas after 24 hours food-deprivation and eight weeks of high-fat diet, showing that both genes were affected by altered food intake in vivo. In conclusion, we propose MFSD4A and MFSD9 to be novel transporters, belonging to disparate SLC families. Both proteins were located to neurons in mouse brain, and their mRNA expression levels were affected by the diet.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- MFSD4A
- MFSD9
- solute carrier
- major facilitator superfamily
- transporter
- homology models
- protein expression
- nutrition.
Publication and Content Type
- ref (subject category)
- art (subject category)
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