Peroxisomal membrane proteins are properly targeted to peroxisomes in the absence of COPI- and COPII-mediated vesicular transport

The classic model for peroxisome biogenesis states that new peroxisomes ari se by the fission of pre-existing ones and that peroxisomal matrix and memb rane proteins are recruited directly from the cytosol. Recent studies chall enge this model and suggest that some peroxisomal membrane proteins might t raffic via the endoplasmic reticulum to peroxisomes. We have studied the tr afficking in human fibroblasts of three peroxisomal membrane proteins, Pex2 p, Pex3p and Pex16p, all of which have been suggested to transit the endopl asmic reticulum before arriving in peroxisomes. Here, we show that targetin g of these peroxisomal membrane proteins is not affected by inhibitors of C OPI and COPII that block vesicle transport in the early secretory pathway. Moreover, we have obtained no evidence for the presence of these peroxisoma l membrane proteins in compartments other than peroxisomes and demonstrate that COPI and COPII inhibitors do not affect peroxisome morphology or integ rity. Together, these data fail to provide any evidence for a role of the e ndoplasmic reticulum in peroxisome biogenesis.