Peroxisome biogenesis: a novel inducible PEX19 splicing variant is involved in early stages of peroxisome proliferation.

Pex19p harbouring a prenylation CAAX box functions as a chaperone and transporter for peroxisomal membrane proteins in membrane assembly. By functional phenotype-complementation assay using a pex19 Chinese hamster ovary cell mutant ZP119, we herein cloned a rat cDNA encoding a protein similar to Pex19p, but with a C-terminal hydrophobic segment in place of the CAAX box region. The transcript of this gene was highly induced by treatment of rats with a peroxisome proliferator, clofibrate, hence termed PEX19i, while the other three less prominently inducible PEX19 variants encoded authentic Pex19p but differed in the length of 3' non-coding region. Pex19pi restored peroxisomes in ZP119 with slightly lower efficiency than Pex19p, showing apparently weaker interaction with Pex11pβ essential for peroxisome proliferation. However, the C-terminal region of Pex19p was not essential for the association of Pex19p with peroxisomal membrane and interaction with membrane assembly factors, Pex3p and Pex16p. Non-prenylated Pex19p interacted with a membrane protein cargo, Pex14p, but more weakly than Pex19pi and the farnesylated Pex19p. Thus, PEX19i most likely plays important roles involving the membrane formation at early stages, in prompt response to peroxisome proliferation. Similar types of PEX19 mRNA variants were also elevated in mouse regenerating liver.