Genetic characterization of C. elegans TMED genes.

Abstract

p24/transmembrane Emp24 domain (TMED) proteins are a set of evolutionarily conserved, single pass transmembrane proteins that have been shown to facilitate protein secretion and selection of cargo proteins to transport vesicles in the cellular secretion pathway. However, their functions in animal development are incompletely understood. The C. elegans genome encodes eight identified TMED genes, with at least one member from each defined subfamily (α, β, γ, δ). TMED gene mutants exhibit a shared set of defects in embryonic viability, animal movement, and vulval morphology. Two γ subfamily genes, tmed-1 and tmed-3, exhibit the ability to compensate for each other, as defects in movement and vulva morphology are only apparent in double mutants. TMED mutants also exhibit a delay in breakdown of basement membrane during vulva development. The results establish a genetic and experimental framework for the study of TMED gene function in C. elegans, and argue that a functional protein from each subfamily is important for a shared set of developmental processes. A specific function for TMED genes is to facilitate breakdown of the basement membrane between the somatic gonad and vulval epithelial cells, suggesting a role for TMED proteins in tissue reorganization during animal development.