Enzymatic insights into an inherited genetic disorder

Abstract

Mutations in an enzyme involved in protein degradation affect a signaling pathway that stimulates the development of the digestive tract.

Keywords: BMP signaling; D. melanogaster; NGLY1; developmental biology; midgut; stem cells.

Figure 1.. The role of NGLY1 in protein processing and development.

(A) In humans and other animals the NGLY1 enzyme removes sugar chains called N-glycans (shown in green and blue) from proteins (purple) that are destined to be degraded via a process known as endoplasmic reticulum-associated degradation (ERAD). If NGLY1 removes a sugar chain from the amino acid asparagine (N), the latter becomes a different amino acid, aspartic acid (D), which may alter the activity of the protein. (B) The equivalent of the NGLY1 enzyme in the fruit fly is known as Pngl. In fruit flies, BMP signaling stimulates the development of the digestive system (left). Homodimers of a BMP ligand called Dpp (red) in a layer of tissue known as the visceral mesoderm (upper layer) activate BMP signaling, which then signals to cells in the endoderm (lower layer). Dpp fails to properly form homodimers in fruit flies with mutations in the Pngl gene, which disrupts BMP signaling within both the visceral mesoderm and the endoderm (right). Cells with active BMP signaling are shown in blue. GlcNAc, N-acetylglucosamine.