8.A.121. The Transmembrane Protein 237 (TMEM237) Family
The apically localized riboflavin (RF) transporter-3 (RFVT-3) is involved in the intestinal absorption of vitamin B2. Transmembrane protein 237 (TMEM237) interacts with the human (h)RFVT-3. TMEM237 is highly expressed in human native intestine and in human intestinal epithelial cell lines, and it co-localizes with hRFVT-3. Expressing TMEM237 caused induction in RF uptake, while its knockdown (with the use of gene-specific siRNA) led to a significant reduction in uptake. Transfecting TMEM237 into HuTu-80 cells also led to a marked enhancement in hRFVT-3 protein stability (reflected by an increase in the protein half-life). Moreover, the level of expression of TMEM237 was reduced following treatment with TNF-alpha (a pro- inflammatory cytokine that inhibits intestinal RF uptake), while its expression was significantly upregulated following treatment with butyrate (an inducer of intestinal RF uptake). Thus, TMEM237 is an interactor with of intestinal hRFVT-3, enhancing its stability and activity (Sabui et al. 2019).