PT  - JOURNAL ARTICLE
AU  - Francesca Di Cara
AU  - Richard A. Rachubinski
AU  - Andrew J. Simmonds
TI  - Functional characterization of peroxisome biogenic proteins Pex5 and Pex7 of <em>Drosophila</em>
AID  - 10.1101/366633
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 366633
4099  - http://biorxiv.org/content/early/2018/07/10/366633.short
4100  - http://biorxiv.org/content/early/2018/07/10/366633.full
AB  - Peroxisomes are ubiquitous membrane-enclosed organelles involved in lipid processing and reactive oxygen detoxification. Mutations in human peroxisome biogenesis genes (Peroxin, PEX) cause progressive developmental disabilities and, in severe cases, 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. Moreover, 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 Pex7 in fly and human. 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.