The Neuronal and Peripheral Expressed Membrane-Bound UNC93A Respond to Nutrient Availability in Mice

Abstract

Many transporters such as the solute carriers belonging to the Major facilitator superfamily Pfam clan are orphans in that their tissue and cellular localization as well as substrate profile and function are still unknown. Here we have characterized the putative solute carrier UNC93A. We aimed to investigate the expression profile on both protein and mRNA level of UNC93A in mouse since it has not been clarified. UNC93A staining was found in cortex, hippocampus and cerebellum. It was found to be expressed in many neurons, but not all, with staining located in close proximity to the plasma membrane. Furthermore, we aimed to extend the starvation data available for Unc93a in hypothalamic cell cultures from mouse. We investigated the Unc93a alterations with focus on amino acid deprivation in embryonic cortex cells from mice as well as 24 h starvation in adult male mice and compared it to recently studied putative and known solute carriers. Unc93a expression was found both in the brain and peripheral organs, in low to moderate levels in the adult mice and was affected by amino acid deprivation in embryonic cortex cultures and starvation in in vivo samples. In conclusion, the membrane-bound UNC93A is expressed in both the brain and peripheral tissues and responds to nutrient availability in mice.

Expanded genetic screening in Caenorhabditis elegans identifies new regulators and an inhibitory role for NAD+ in axon regeneration

“…Additionally, we found that MFSD-6, a member of the Major Facilitator Superfamily Domain (MFSD) family, promotes PLM regrowth ( Figure 1—figure supplement 2F ). MFSD family proteins have 10–12 transmembrane regions ( Yan, 2015 ); some mediate nutrient transport across the blood-brain barrier ( Ceder et al, 2017 ; Perland et al, 2017 ), but most are of unknown function. C. elegans MFSD-6 was previously identified as a regulator of motor circuit activity and mfsd-6(0) mutants are resistant to inhibitors of cholinesterase ( McCulloch et al, 2017 ).…”

CG4928 Is Vital for Renal Function in Fruit Flies and Membrane Potential in Cells: A First In-Depth Characterization of the Putative Solute Carrier UNC93A

“…The ortholog found in C. elegan s is suggested to be a regulatory protein of a potassium channel ( de la Cruz et al, 2003 ). Interestingly, there is also evidence that UNC93A is a membrane-bound protein ( Levin and Horvitz, 1992 ; Liu et al, 2002 ; Ceder et al, 2017 ) with a 2D topology resembling an authentic transporter according to predictions ( Ceder et al, 2017 ; Perland et al, 2017a ). In D. melanogaster , the ortholog CG4928 was found to be highly expressed in the Malpighian tubules, equivalent to the human kidneys ( Wang et al, 2004 ), to be important for hemocyte development ( Stofanko et al, 2008 ), and to be one of several genes that confer manganese toxicity resistance ( Mohr et al, 2018 ).…”

“…Members of the MFS are facilitators and secondary active transporters with various expressions, functions, and substrate profiles ( Pao et al, 1998 ; Reddy et al, 2012 ). Like many SLCs of MFS type, UNC93A is evolutionary conserved ( Ceder et al, 2017 ).…”

“…Studies on UNC93A have been performed using Caenorhabditis elegans ( Levin and Horvitz, 1992 ; de la Cruz et al, 2003 ), Aedes aegypti ( Campbell et al, 2011 ), Drosophila melanogaster ( Wang et al, 2004 ; Stofanko et al, 2008 ; Mohr et al, 2018 ; Ceder et al, 2020 ), Anguilla anguilla ( Kalujnaia et al, 2007 ), Mus musculus ( Ceder et al, 2017 , 2020 ; Perland and Fredriksson, 2017 ; Perland et al, 2017a ), and humans ( Liu et al, 2002 ; Son et al, 2015 ; Schlosser et al, 2020 ), but a majority of these studies are not focusing on the localization and/or the function of UNC93A. The ortholog found in C. elegan s is suggested to be a regulatory protein of a potassium channel ( de la Cruz et al, 2003 ).…”

“…Recently, we confirmed that UNC93A is evolutionary conserved in mammals and found that it is expressed in metabolic active organs such as the brain and the kidneys. Furthermore, Unc93a and CG4928 are affected by dietary restrictions and starvation in mice and fruit flies ( Ceder et al, 2017 , 2020 ). The role of UNC93A and its implications in processes, such as homeostasis and pathology, are not completely known, and to explore its role in humans would be difficult and time consuming.…”