ZFIN ID: ZDB-PUB-080422-17
Goodpasture antigen-binding protein and its spliced variant, ceramide transfer protein, have different functions in the modulation of apoptosis during zebrafish development
Granero-Moltó, F., Sarmah, S., O'Rear, L., Spagnoli, A., Abrahamson, D., Saus, J., Hudson, B.G., and Knapik, E.W.
Date: 2008
Source: The Journal of biological chemistry   283(29): 20495-20504 (Journal)
Registered Authors: Knapik, Ela W., Sarmah, Swapnalee
Keywords: none
MeSH Terms:
  • Alternative Splicing/genetics*
  • Amino Acid Sequence
  • Animals
  • Apoptosis*
  • Autoantigens/chemistry
  • Autoantigens/genetics
  • Autoantigens/immunology
  • Autoantigens/metabolism*
  • Cell Line
  • Ceramides/metabolism
  • Cloning, Molecular
  • Collagen Type IV/chemistry
  • Collagen Type IV/genetics
  • Collagen Type IV/immunology
  • Collagen Type IV/metabolism*
  • DNA, Complementary/genetics
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/embryology
  • Embryo, Nonmammalian/metabolism
  • Gene Expression Regulation, Developmental*
  • Humans
  • Molecular Sequence Data
  • Phenotype
  • Protein Binding
  • Protein Isoforms/genetics
  • Protein Isoforms/metabolism
  • Protein Serine-Threonine Kinases/genetics
  • Protein Serine-Threonine Kinases/metabolism*
  • RNA, Messenger/genetics
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 18424781 Full text @ J. Biol. Chem.
Human Goodpasture antigen-binding protein (GPBP) is an atypical protein kinase that phosphorylates the Goodpasture auto-antigen, the a3 chain of collagen IV. The COL4A3BP gene is alternatively spliced producing two protein isoforms: GPBP and GPBP26. The latter lacks a serine-rich domain composed of 26 amino acid residues. Both isoforms also function as ceramide transfer proteins (CERT). Here, we explored the function of Gpbp and Gpbp26/CERT during embryogenesis in zebrafish. We cloned both splice variants of the zebrafish gene, and found that they are differentially expressed during development. We used antisense oligonucleotide-mediated loss-of-function and synthetic mRNA-based gain-of-function approaches. Our results show that the loss-of-function phenotype is linked to cell death, evident primarily in the muscle of the somites, extensive loss of myelinated tracks and brain edema. These results indicate that disruption of the non-vesicular ceramide transport is detrimental to normal embryonic development of somites and brain due to increased apoptosis. Moreover, this phenotype is mediated by Gpbp but not Gpbp26/CERT, suggesting that Gpbp is an important factor for normal skeletal muscle and brain development.