TY - JOUR
T1 - Goodpasture antigen-binding protein and its spliced variant, ceramide transfer protein, have different functions in the modulation of apoptosis during zebrafish development
AU - Granero-Moltó, Froilán
AU - Sarmah, Swapnalee
AU - O'Rear, Lynda
AU - Spagnoli, Anna
AU - Abrahamson, Dale
AU - Saus, Juan
AU - Hudson, Billy G.
AU - Knapik, Ela W.
PY - 2008/7/18
Y1 - 2008/7/18
N2 - Human Goodpasture antigen-binding protein (GPBP) is an atypical protein kinase that phosphorylates the Goodpasture auto-antigen, the α3 chain of collagen IV. The COL4A3BP gene is alternatively spliced producing two protein isoforms: GPBP and GPBPΔ26. 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 GpbpΔ26/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 nonvesicular ceramide transport is detrimental to normal embryonic development of somites and brain because of increased apoptosis. Moreover, this phenotype is mediated by Gpbp but not GpbpΔ26/CERT, suggesting that Gpbp is an important factor for normal skeletal muscle and brain development.
AB - Human Goodpasture antigen-binding protein (GPBP) is an atypical protein kinase that phosphorylates the Goodpasture auto-antigen, the α3 chain of collagen IV. The COL4A3BP gene is alternatively spliced producing two protein isoforms: GPBP and GPBPΔ26. 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 GpbpΔ26/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 nonvesicular ceramide transport is detrimental to normal embryonic development of somites and brain because of increased apoptosis. Moreover, this phenotype is mediated by Gpbp but not GpbpΔ26/CERT, suggesting that Gpbp is an important factor for normal skeletal muscle and brain development.
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U2 - 10.1074/jbc.M801806200
DO - 10.1074/jbc.M801806200
M3 - Article
C2 - 18424781
AN - SCOPUS:50649122795
SN - 0021-9258
VL - 283
SP - 20495
EP - 20504
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 29
ER -