Pex7, a shuttling receptor, is crucial for importing matrix proteins with a type 2 peroxisomal targeting signal (PTS2) to peroxisomes [2,3,4]. Peroxisomes are involved in lipid processing, reactive oxygen detoxification, and other metabolic processes, making Pex7 essential for these biological functions [5]. Genetic models, like KO mouse models, are valuable for studying Pex7.

In a Pex7-deficient mouse series, different genotypes (homozygous hypomorphic, compound heterozygous, and homozygous null) showed a graded reduction in plasmalogen (Pls) levels and increases in C26:0-LPC and phytanic acid (PA) in plasma and brain. These mice also had neuropathological changes such as loss of cerebellar Purkinje cells and decreased myelin basic protein, along with hyperactive behavior and reduced brain neurotransmitter levels. The study demonstrated a genotype-phenotype correlation between Pex7 deficiency severity and various clinical and neurobiochemical phenotypes in Rhizomelic chondrodysplasia punctata type 1 (RCDP1) [1].

In conclusion, Pex7 is vital for the peroxisomal import of PTS2-containing proteins and thus for normal peroxisomal function. The Pex7-deficient mouse models have revealed its role in RCDP1, showing how Pex7 deficiency can lead to biochemical and neurobehavioral changes. This understanding can contribute to further research on RCDP1 and potentially other related peroxisomal disorders.

References:

1. Fallatah, Wedad, Cui, Wei, Di Pietro, Erminia, Berger, Johannes, Braverman, Nancy E. 2022. A Pex7 Deficient Mouse Series Correlates Biochemical and Neurobehavioral Markers to Genotype Severity-Implications for the Disease Spectrum of Rhizomelic Chondrodysplasia Punctata Type 1. In Frontiers in cell and developmental biology, 10, 886316. doi:10.3389/fcell.2022.886316. https://pubmed.ncbi.nlm.nih.gov/35898397/

2. Shin, Jong-Hwan, Fu, Teng, Kim, Kyoung Su. 2021. Pex7 selectively imports PTS2 target proteins to peroxisomes and is required for anthracnose disease development in Colletotrichum scovillei. In Fungal genetics and biology : FG & B, 157, 103636. doi:10.1016/j.fgb.2021.103636. https://pubmed.ncbi.nlm.nih.gov/34742890/

3. Lin, Mei, Abubakar, Yakubu Saddeeq, Wei, Lijing, Zhou, Jie, Yu, Wenying. 2022. Fusarium verticillioides Pex7/20 mediates peroxisomal PTS2 pathway import, pathogenicity, and fumonisin B1 biosynthesis. In Applied microbiology and biotechnology, 106, 6595-6609. doi:10.1007/s00253-022-12167-8. https://pubmed.ncbi.nlm.nih.gov/36121485/

4. Rodrigues, Tony A, Alencastre, Inês S, Francisco, Tânia, Grou, Cláudia P, Azevedo, Jorge E. 2014. A PEX7-centered perspective on the peroxisomal targeting signal type 2-mediated protein import pathway. In Molecular and cellular biology, 34, 2917-28. doi:10.1128/MCB.01727-13. https://pubmed.ncbi.nlm.nih.gov/24865970/

5. Di Cara, Francesca, Rachubinski, Richard A, Simmonds, Andrew J. 2018. Distinct Roles for Peroxisomal Targeting Signal Receptors Pex5 and Pex7 in Drosophila. In Genetics, 211, 141-149. doi:10.1534/genetics.118.301628. https://pubmed.ncbi.nlm.nih.gov/30389805/