TRAM-LAG1-CLN8 domain-containing protein TMEM56 regulates cell migration by changing intracellular ceramide levels

Abstract Background Cell migration is a fundamental biological process essential for embryonic development and hematopoiesis. In a shRNA screen, we identified the TRAM-LAG1-CLN8 domain-containing transmembrane protein TMEM56 as a previously uncharacterized regulator of stromal cell-derived factor 1 (SDF-1)-mediated cell migration. This study investigates the molecular mechanisms underlying TMEM56 function. Results TMEM56 is expressed in both murine embryonic and adult tissues, with enrichment in hematopoietic stem and erythroid progenitor cells. Lipidomic analysis reveals that TMEM56 modulates ceramide metabolism, particularly affecting levels of hexosylated ceramides. Co-immunoprecipitation assays indicate that TMEM56 physically interacts with ceramide synthase 2 (CerS2), suggesting a role in lipid signaling pathways. Conclusion Our findings identify TMEM56 as a key regulator of cell migration, linking lipid metabolism with hematopoietic and developmental processes. These results provide novel insights into the molecular mechanisms governing migration.