Abstract

BackgroundSolute carriers (SLCs) are membrane bound transporters responsible for the movement of soluble molecules such as amino acids, ions, nucleotides, neurotransmitters and oligopeptides over cellular membranes. At present, there are 395 SLCs identified in humans, where about 40% are still uncharacterized with unknown expression and/or function(s). Here we have studied two uncharacterized atypical SLCs that belong to the Major Facilitator Superfamily Pfam clan, Major facilitator superfamily domain 5 (MFSD5) and Major facilitator superfamily domain 11 (MFSD11). We provide fundamental information about the histology in mice as well as data supporting their disposition to regulate expression levels to keep the energy homeostasis.ResultsIn mice subjected to starvation or high-fat diet, the mRNA expression of Mfsd5 was significantly down-regulated (P<0.001) in food regulatory brain areas whereas Mfsd11 was significantly up-regulated in mice subjected to either starvation (P<0.01) or high-fat diet (P<0.001). qRT-PCR analysis on wild type tissues demonstrated that both Mfsd5 and Mfsd11 have a wide central and peripheral mRNA distribution, and immunohistochemistry was utilized to display the abundant protein expression in the mouse embryo and the adult mouse brain. Both proteins are expressed in excitatory and inhibitory neurons, but not in astrocytes.ConclusionsMfsd5 and Mfsd11 are both affected by altered energy homeostasis, suggesting plausible involvement in the energy regulation. Moreover, the first histological mapping of MFSD5 and MFSD11 shows ubiquitous expression in the periphery and the central nervous system of mice, where the proteins are expressed in excitatory and inhibitory mouse brain neurons.

Highlights

  • Among all proteins in the human genome around 27% are membrane bound [1], and within this group the solute carriers (SLCs) are the second largest family consisting of at least 395 members in humans [2]

  • In mice subjected to starvation or high-fat diet, the mRNA expression of Major facilitator superfamily domain 5 (Mfsd5) was significantly down-regulated (P

  • Mfsd5 and Mfsd11 are both affected by altered energy homeostasis, suggesting plausible involvement in the energy regulation

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Summary

Introduction

Among all proteins in the human genome around 27% are membrane bound [1], and within this group the solute carriers (SLCs) are the second largest family consisting of at least 395 members in humans [2]. The majority of the mammalian SLC proteins can be classified into three Pfam clans based on sequence homology; the major facilitator superfamily (MFS), amino acid- polyamine organocation (APC) and the monovalent cation:proton antiporter (CPA)/anion transporter (AT) clan [5]. The MFS clan is one of the largest groups of phylogenetically related membrane proteins [6] and the largest group of phylogenetically related SLCs in humans [5]. It is one of the most functionally diverse superfamilies among the transporter proteins [6,7]. We provide fundamental information about the histology in mice as well as data supporting their disposition to regulate expression levels to keep the energy homeostasis

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