Resumen
Peroxisomes are ubiquitous membrane-enclosed organelles involved in lipid processing and reactive oxygen detoxification. Mutations in human peroxisome biogenesis genes (Peroxin, PEX, orPex) cause developmental disabilities and often early death. Pex5 and Pex7 are receptors that recognize different peroxisomal targeting signals called PTS1 and PTS2, respectively, and traffic proteins to the peroxisomal matrix. We characterized mutants of Drosophila melanogaster Pex5 and Pex7 and found that adult animals are affected in lipid processing. Pex5 mutants exhibited severe developmental defects in the embryonic nervous system and muscle, similar to what is observed in humans with PEX5 mutations, while Pex7 fly mutants were weakly affected in brain development, suggesting different roles for fly Pex7 and human PEX7. Of note, although no PTS2-containing protein has been identified in Drosophila, Pex7 from Drosophila can function as a bona fide PTS2 receptor because it can rescue targeting of the PTS2-containing protein thiolase to peroxisomes in PEX7 mutant human fibroblasts.
Idioma original | English |
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Páginas (desde-hasta) | 141-149 |
Número de páginas | 9 |
Publicación | Genetics |
Volumen | 211 |
N.º | 1 |
DOI | |
Estado | Published - ene. 2019 |
Nota bibliográfica
Funding Information:We thank Nancy E. Braverman (McGill University) for advice and for providing wild-type and RCDP1 human fibroblasts; and the Lipidomics Core Facility at the University of Alberta, which is supported by funding from the Faculty of Medicine & Dentistry and the Women and Children’s Health Research Institute, University of Alberta. This work was funded by a Collaborative Research Innovation Opportunities grant from Alberta Innovates ‒ Health Solutions to R.A.R. and A.J.S., a Canadian Institutes of Health Research Foundation grant 143289 to R.A.R., and charitable support from The Edgar Foundation and the Ladies Auxiliary of the Fraternal Order of Eagles 3395 to R.A.R.
Publisher Copyright:
© 2019 by the Genetics Society of America.
ASJC Scopus Subject Areas
- Genetics