Multiple distinct targeting signals in integral peroxisomal membrane proteins

Peroxisomal proteins are synthesized on free polysomes and then transported from the cytoplasm to peroxisomes. This process is mediated by two short w ell-defined targeting signals in peroxisomal matrix proteins, but a well-de fined targeting signal has not yet been described for peroxisomal membrane proteins (PMPs). One assumption in virtually all prior studies of PMP targe ting is that a given protein contains one, and only one, distinct targeting signal. Here, we show that the metabolite transporter PMP34, an integral P MP, contains at least two nonoverlapping sets of targeting information, eit her of which is sufficient for insertion into the peroxisome membrane. We a lso show that another integral PMP, the peroxin PEX13, also contains two in dependent sets of peroxisomal targeting information. These results challeng e a major assumption of most PMP targeting studies. In addition, we demonst rate that PEX19, a factor required for peroxisomal membrane biogenesis, int eracts with the two minimal targeting regions of PMP34. Together, these res ults raise the interesting possibility that PMP import may require novel me chanisms to ensure the solubility of integral PMPs before their insertion i n the peroxisome membrane, and that PEX19 may play a central role in this p rocess.