Which step of the cytotoxic pathway is regulated by EBAG9?
Rüder and colleagues used various approaches to determine which step of cytotoxic granule biogenesis is regulated by EBAG9 expression (11). Their findings provide compelling evidence that EBAG9 does not directly regulate the secretion of secretory lysosomes, but rather acts upstream of the exocytic process, in the trafficking of the cytotoxic components along the endosomal-lysosomal pathway. They observed that the loss of EBAG9 enhanced the sorting of granzyme B and of the acid hydrolase cathepsin D to the secretory lysosomes. In contrast, the sorting of lysosomal membrane marker LAMP1, which uses an AP-dependent pathway, was reduced in EBAG9-deficient cells. Interestingly, they report (although this data is not shown) that the sorting of perforin was also enhanced, suggesting that the sorting of perforin may occur via the same trafficking pathway as the sorting of granzymes. A role for EBAG9 in the trafficking between endosomal and lysosomal compartments is further supported by the fi
