The Fly Homologue of MFSD11 Is Possibly Linked to Nutrient Homeostasis and Has a Potential Role in Locomotion: A First Characterization of the Atypical Solute Carrier CG18549 in Drosophila Melanogaster

SIMPLE SUMMARY: The body is dependent on nutrients and ions to work normally. Within the hu-man body there is a group of proteins named transporters or solute carriers. These transporters are vital for the transport of nutrients such as glucose, amino acids, and fats, as well as ions such as sodium, calcium, and potassium. Despite being vital for normal physiology, as well as pathophysiology, a large number (approximately one third) of the transporters are orphans, where information about their expression and function is missing. Here, we aimed to begin to unravel the expression and function of one of these orphan transporters, MFSD11, by studying its orthologue in fruit flies (CG18549). We found that the fly orthologue is expressed in the brain of fruit flies and that it is possibly involved in metabolism and/or locomotion of the flies. The exact mechanism behind the observed behaviors is not fully understood, but our study provides new insights into the expression and function of CG18549. Clearly, these results, among others about the orphan transporters, provide a strong example as to why it is vital to fully characterize them and through that gain knowledge about the body during normal condition and disease. ABSTRACT: Cellular transport and function are dependent on substrate influx and efflux of various compounds. In humans, the largest superfamily of transporters is the SoLute Carriers (SLCs). Many transporters are orphans and little to nothing is known about their expression and/or function, yet they have been assigned to a cluster called atypical SLCs. One of these atypical SLCs is MFSD11. Here we present a first in-depth characterization of the MFSD11, CG18549. By gene expression and behavior analysis on ubiquitous and brain-specific knockdown flies. CG18549 knockdown flies were found to have altered adipokinetic hormone and adipokinteic hormone receptor expression as well as reduced vesicular monoamine transporter expression; to exhibit an altered locomotor behavior, and to have an altered reaction to stress stimuli. Furthermore, the gene expression of CG18549 in the brain was visualized and abundant expression in both the larvae and adult brain was observed, a result that is coherent with the FlyAtlas Anatomy microarray. The exact mechanism behind the observed behaviors is not fully understood, but this study provides new insights into the expression and function of CG18549. Clearly, these results provide a strong example as to why it is vital to fully characterize orphan transporters and through that gain knowledge about the body during normal condition and disease.