Mucin-type O-glycosylation is required for digestive system formation and function in Drosophila

Monday, October 24, 2011 — Poster Session I
Noon – 2:00 p.m.	Natcher Conference Center	NIDCR	DEV-13

Authors

• L Zhang
• K Ten Hagen

Abstract

Mucins are high molecular weight glycoproteins that serve as the main constituent of the mucus-protective layer lining the gastrointestinal tract, conferring protection from chemical, microbiological and mechanical damage. The glycosylation of mucins is initiated by a family of glycosyltransferases encoded by the pGalNAcT genes in mammals and pgant genes in Drosophila. Here we demonstrate that one pgant member, pgant4, is required for digestive system formation and function in Drosophila. pgant4 is expressed specifically in a subset of foregut cells (PR cells) that are responsible for secreting the peritrophic membrane of the digestive system. Mutations in pgant4 or RNAi to pgant4 result in lethality. pgant4 mutant larvae displayed abnormal proventriculus formation, with larger and irregularly-shaped PR cells. Immunostaining revealed that one peritrophic membrane protein accumulated in the mutant PR cells. Western blotting showed loss of O-glycoproteins in the mutant foregut. We propose that PGANT4 is responsible for glycosylating certain mucin proteins within gastrointestinal tract which play important roles in establishing digestive system structure and function. This study provides new evidence that mucin-type O-glycosylation is required for digestive system function and a new platform to investigate the relationship between abnormal O-glycosylation and the predisposition to colitis and colon cancer seen in mammals.

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