Human Pex19p Binds Peroxisomal Integral Membrane Proteins at Regions Distinct from Their Sorting Sequences

Abstract

The molecular machinery underlying peroxisomal membrane biogenesis is not well understood. The observation that cells deficient in the peroxins Pex3p, Pex16p, and Pex19p lack peroxisomal membrane structures suggests that these molecules are involved in the initial stages of peroxisomal membrane formation. Pex19p, a predominantly cytosolic protein that can be farnesylated, binds multiple peroxisomal integral membrane proteins, and it has been suggested that it functions as a soluble receptor for the targeting of peroxisomal membrane proteins (PMPs) to the peroxisome. An alternative view proposes that Pex19p functions as a chaperone at the peroxisomal membrane. Here, we show that the peroxisomal sorting determinants and the Pex19p-binding domains of a number of PMPs are distinct entities. In addition, we extend the list of peroxins with which human Pex19p interacts to include the PMP Pex16p and show that Pex19p's CaaX prenylation motif is an important determinant in the affinity of Pex19p for Pex10p, Pex11pβ, Pex12p, and Pex13p.

ACKNOWLEDGMENTS

We are grateful to Y. Sakai (Kyoto, Japan) and M. Baes (Leuven, Belgium) for the pEGFPH1 plasmid and the anti-Pex5p antiserum, respectively. The help of Jeroen Van Looy, Vanessa Brys, and Ilse Broekaert is highly appreciated.

M. Fransen is a postdoctoral fellow of the Fonds voor Wetenschappelijk Onderzoek-Vlaanderen (FWO). This work was supported by a Geconcerteerde Onderzoeksacties grant (GOA/99/09) from the Flemish government.