Mouse PeP: A novel peroxisomal protein linked to myoblast differentiation and development

Abstract

The identification of several peroxisomal proteins in the past decade has deepened our understanding of the biology of peroxisomes and their involvement in human disorders. We report the cloning and expression pattern during the mouse development of a cDNA encoding a novel protein, named PeP, and show that its product is imported specifically to the peroxisome matrix in a variety of cell types. We also demonstrate that PeP is imported to the organelle through the PEX5 receptor pathway, which indicates that the C-terminal tripeptide SKI behaves as a type 1 peroxisomal targeting signal (PTS1). PeP expression is tightly regulated, as shown by Northern and in situ hybridization experiments. Thus during embryonic development in the mouse, PeP mRNA is detected almost exclusively in the skeletal muscle, whereas in adult mice, strong expression is also found in the heart and brain. In addition, PeP mRNA accumulation is induced after myoblast differentiation in vitro, when myotube formation is promoted. Sequence analysis reveals that PeP has no significant homology to any known protein, except for a short stretch of amino acids containing the fingerprint of the fibronectin type III superfamily, a domain present in proteins often related to molecular and cellular recognition and binding processes. Thus our data suggest a connection between the function of PeP and murine cell differentiation and development.

SMAD3 Negatively Regulates Serum Irisin and Skeletal Muscle FNDC5 and Peroxisome Proliferator-activated Receptor γ Coactivator 1-α (PGC-1α) during Exercise

“…Other studies suggest that irisin may induce browning centrally through a PGC-1␣ estrogen-related receptor-␣ BDNF pathway (19,20). Irisin is a cleavage product of the membrane protein FNDC5 (fibronectin type III domain containing 5) (21,22) and is a PGC-1␣-regulated hormone secreted from skeletal muscle cells dur-* This work was supported, in whole or in part, by the National Institutes of Health intramural program. 1 ing (or following) exercise (16).…”

Evidence against a beneficial effect of irisin in humans

“…Overexpression of PGC1a in mice skeletal muscle as well as exercise induced expression of the FNDC5 gene [21], a gene which has scarcely been studied before. In 2002 two different groups first described the mouse sequence of FNDC5 [22,23]. In adult murine tissues, FNDC5 is highly expressed in heart and brain and less in skeletal muscle [22,23].…”

“…In 2002 two different groups first described the mouse sequence of FNDC5 [22,23]. In adult murine tissues, FNDC5 is highly expressed in heart and brain and less in skeletal muscle [22,23]. FNDC5 is described as a protein containing a signal peptide, fibronectin type III repeats, and hydropathy analysis revealed a hydrophobic region, which is likely to encode a transmembrane domain.…”

“…FNDC5 is described as a protein containing a signal peptide, fibronectin type III repeats, and hydropathy analysis revealed a hydrophobic region, which is likely to encode a transmembrane domain. Previous studies linked the gene to differentiation of myoblasts and neurones [23,24], and it has been suggested that FNDC5 is located in the matrix of peroxisomes [23]. However, Boström et al showed that the transmembrane protein is cleaved by transfected HEK293 cells and the extracellular part of the protein is released, which acts as novel molecule called irisin [21].…”

Irisin and Fibronectin Type III Domain-Containing 5 Responses to Exercise in Different Environmental Conditions

“…FNDC5 is a single peptide transmembrane protein inserted into the cellular membrane of skeletal muscle and WAT (10,31) and was discovered in 2002 prior to irisin (8). Due to BAT's increased mitochondria density, peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), which is highly expressed in tissues with high mitochondrial density, has been thought to regulate the expression of FNDC5, thus regulating irisin.…”