8.A.187.  The Podocalyxin (PODXL) Family 

Podocalyxin (PODXL) is a highly sialylated transmembrane protein that is expressed on the luminal membrane of brain microvascular endothelial cells that may function in the blood-brain barrier (BBB).   PODXL-knockdown affected the expression of ABCB1/MDR1, in human microvascular endothelial cells (hCMEC/D3). PODXL-knockdown influenced the immune response and intracellular trafficking. Among transporters, the protein expression of ABCB1/MDR1 and ABCG2/BCRP was elevated by approximately 2-fold in the PODXL-knockdown cells, and the efflux activity of ABCB1/MDR1 was increased. Levels of occludin was increased, while those of claudin-11 were decreased in the knockdown cells. Thus, PODXL functions as a modulator of BBB function, including transport, tight junctions, and immune responses. Furthermore, PODXL post-transcriptionally regulates the protein expression and efflux activity of ABCB1/MDR1 at the BBB (Nagano et al. 2022).