Goodpasture antigen-binding protein and its spliced variant, ceramide transfer protein, have different functions in the modulation of apoptosis during zebrafish development

Froilán Granero-Moltó, Swapnalee Sarmah, Lynda O'Rear, Anna Spagnoli, Dale Abrahamson, Juan Saus, Billy G. Hudson, Ela W. Knapik

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)20495-20504
Number of pages10
JournalJournal of Biological Chemistry
Volume283
Issue number29
DOIs
StatePublished - Jul 18 2008
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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