| RRC ID |
21850
|
| Author |
Ayukawa T, Matsumoto K, Ishikawa HO, Ishio A, Yamakawa T, Aoyama N, Suzuki T, Matsuno K.
|
| Title |
Rescue of Notch signaling in cells incapable of GDP-L-fucose synthesis by gap junction transfer of GDP-L-fucose in Drosophila.
|
| Journal |
Proc Natl Acad Sci U S A
|
| Abstract |
Notch (N) is a transmembrane receptor that mediates cell-cell interactions to determine many cell-fate decisions. N contains EGF-like repeats, many of which have an O-fucose glycan modification that regulates N-ligand binding. This modification requires GDP-L-fucose as a donor of fucose. The GDP-L-fucose biosynthetic pathways are well understood, including the de novo pathway, which depends on GDP-mannose 4,6 dehydratase (Gmd) and GDP-4-keto-6-deoxy-D-mannose 3,5-epimerase/4-reductase (Gmer). However, the potential for intercellularly supplied GDP-L-fucose and the molecular basis of such transportation have not been explored in depth. To address these points, we studied the genetic effects of mutating Gmd and Gmer on fucose modifications in Drosophila. We found that these mutants functioned cell-nonautonomously, and that GDP-L-fucose was supplied intercellularly through gap junctions composed of Innexin-2. GDP-L-fucose was not supplied through body fluids from different isolated organs, indicating that the intercellular distribution of GDP-L-fucose is restricted within a given organ. Moreover, the gap junction-mediated supply of GDP-L-fucose was sufficient to support the fucosylation of N-glycans and the O-fucosylation of the N EGF-like repeats. Our results indicate that intercellular delivery is a metabolic pathway for nucleotide sugars in live animals under certain circumstances.
|
| Volume |
109(38)
|
| Pages |
15318-23
|
| Published |
2012-9-18
|
| DOI |
10.1073/pnas.1202369109
|
| PII |
1202369109
|
| PMID |
22949680
|
| PMC |
PMC3458340
|
| MeSH |
Alleles
Animals
Carbohydrate Epimerases / metabolism*
Drosophila / metabolism*
Epidermal Growth Factor / metabolism
Fucose / chemistry
Gap Junctions / metabolism*
Gene Expression Regulation
Gene Expression Regulation, Enzymologic
Guanosine Diphosphate Fucose / chemistry*
Homozygote
Hydro-Lyases / metabolism*
Models, Genetic
Mutation
Phenotype
Receptors, Notch / metabolism*
Recombination, Genetic
|
| IF |
9.412
|
| Times Cited |
15
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| Drosophila |
8890R-2 |
