Bacterial symbionts induce a FUT2-dependent fucosylated niche on colonic epithelium via ERK and JNK signaling.
The intestinal epithelium of the adult gut supports a complex, dynamic microbial ecosystem and expresses highly fucosylated glycans on its surface. Uncolonized gut contains little fucosylated glycan. The transition toward adult colonization, such as during recovery from germ-free status or from antibiotic treatment, increased expression of fucosylated epitopes in the colonic epithelium. This increase in fucosylation is accompanied by induction of fut2 mRNA expression and alpha1,2/3-fucosyltransferase activity. Colonization stimulates ERK and JNK signal transduction pathways, resulting in activation of transcription factors ATF2 and c-Jun, respectively. This increases transcription of fut2 mRNA and expression of alpha1,2/3-fucosyltransferase activity, resulting in a highly fucosylated intestinal mucosa characteristic of the adult mammalian gut. Blocking the ERK and JNK signaling cascade inhibits the ability of colonization to induce elevated fut2 mRNA and fucosyltransferase activity in the mature colon. Thus pioneer-mutualist symbiotic bacteria may utilize the ERK and JNK signaling cascade to induce the high degree of fucosylation characteristic of adult mammalian colon, and we speculate that this fucosylation facilitates colonization by adult microbiota.
Meng
Di
D
Developmental Gastroenterology Laboratory, Massachusetts General Hospital-East, 114 16th St., Rm 3650, Charlestown, MA 02129, USA.
Newburg
David S
DS
Young
Cheryl
C
Baker
Amy
A
Tonkonogy
Susan L
SL
Sartor
R Balfour
RB
Walker
W Allan
WA
Nanthakumar
N Nanda
NN
D000818:Animals; D003106:Colon / Q000382:microbiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D005647:Fucosyltransferases / Q000502:physiology*; D005856:Germ-Free Life; D007413:Intestinal Mucosa / Q000382:microbiology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*; D051379:Mice; D015398:Signal Transduction / Q000502:physiology*; D013559:Symbiosis; D000097631:Galactoside 2-alpha-L-fucosyltransferase
D048049:Extracellular Signal-Regulated MAP Kinases; D005647:Fucosyltransferases; D048031:JNK Mitogen-Activated Protein Kinases; D000097631:Galactoside 2-alpha-L-fucosyltransferase