Protein trafficking‐ a road map for embryogenesis

Abstract

Transmembrane Emp24 domain trafficking protein (TMED) 2, a member of the p24 family of chaperones is involved in protein transport between the ER and Golgi. TMED2 complexes with TMED7, TMED9 and TMED10 and is required for normal levels of these proteins. Loss of Tmed2 results in delayed and abnormal development of homozygous mutant mouse embryos and placentas, loss of TMED7 and TMED10, and decreased expression of TMED9 protein. In Tmed2 mutant embryos, the labyrinth layer of the placenta - the site of gas and nutrient exchanges between the mother and the fetus - fails to form. Formation of the labyrinth layer depends on proper differentiation of the syncytiotrophoblast cells that separate the maternal and fetal environment. The choriocarcinoma cell lines BeWo and JEG-3 were used to examine TMED2 expression and function during trophoblast differentiation. These cells share some properties in terms of biochemical markers and hormone secretion. However, only BeWo cells fuse to form syncytiotrophoblasts. The aim of this study was to determine if TMED2 was expressed in human placenta and was required during trophoblast differentiation. In 1st trimester placentas, TMED2 was expressed in cytotrophoblast stem cells and in differentiated syncytiotrophoblasts. In the choriocarcinoma cell lines, we observed 60-fold more TMED2 mRNA and protein levels in BeWo when compared with JEG-3 cells. BeWo cells also expressed significantly higher levels of TMED7 and TMED10 mRNA. TMED2 was localized to the ER-Golgi intermediate compartment and was upregulated during differentiation of BeWo cells into syncytiotrophoblasts. Our results show that TMED2, TMED7, and TMED10 are highly expressed in human placentas and suggest a role for these proteins during syncytiotrophoblast differentiation. This work was supported by operating grants from NSERC and CIHR.