Complementary and divergent roles for Ctage5 and Tango1 in zebrafish

Abstract

Coat protein complex II (COPII) factors mediate cargo export from the endoplasmic reticulum (ER), but bulky collagens and lipoproteins are too large for traditional COPII vesicles. Mammalian CTAGE5 and TANGO1 have been well characterized individually as specialized cargo receptors at the ER that function with COPII coats to facilitate trafficking of bulky cargoes. Here, we present a genetic interaction study in zebrafish of deletions in ctage5, tango1, or both to investigate their potential distinct and complimentary functions. We found that Ctage5 and Tango1 have different roles related to organogenesis, collagen versus lipoprotein trafficking, stress-pathway activation, and survival. While deletion of both ctage5 and tango1 compounded phenotype severity, deletion of either factor alone revealed novel tissue specific defects in the building of heart, muscle, lens, and intestine, in addition to the previously described roles in the development of neural and cartilage tissues. Together, our results suggest that Ctage5 and Tango1 have overlapping, but also divergent roles in tissue development and homeostasis. SummaryIn this genetic study Ctage5 and Tango1 endoplasmic reticulum cargo receptors were investigated together in vivo for the first time. Cell differentiation, survival, trafficking, and stress pathway activation were investigated.