Premium
All in the family: the role of the UDP N‐acetylgalactosamine polypeptide: alpha‐N‐acetylgalactosaminyltransferases (ppGalNAc T’s) in development and disease in the craniofacial complex
Author(s) -
Tabak Lawrence A.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a421-a
Subject(s) - biology , phenotype , craniofacial , gene isoform , drosophila melanogaster , microbiology and biotechnology , mutation , drosophila (subgenus) , genetics , immunology , gene
It remains puzzling why so many different ppGalNAc T’s are required to decorate the Ser/Thr residues of proteins with GalNAc. Conserved throughout much of evolution, family members are expressed in spatially and temporally specific fashion during mouse, worm and fly development. At least one Drosophila isoform, pgant35A, (the Drosophila orthologue of mammalian ppGalNAc T‐11) is required for normal fly development since mutations within the coding region result in a recessive lethal phenotype during early pupal development. Recent work with mouse models point to multiple functional roles related to systems as diverse as bone development and innate and adaptive immunity. In ppGalNAc T‐1 deficient mice our laboratory has recently observed a significant delay in skeletal development in a subset of late stage embryos. Examples of human pathobiology are now emerging. Mutations in GALNT3 have recently been shown to result in familial tumoral calcinosis ‐ a severe metabolic disorder that results in the deposition of calcium deposits in subcutaneous tissues. Taken together, it appears that the “simple” transfer of GalNAc is shrouded with many secrets that have yet to be uncovered.