The peroxisome biogenesis factors posttranslationally target reticulon homology domain-containing proteins to the endoplasmic reticulum membrane

The endoplasmic reticulum (ER) is shaped by a class of membrane proteins containing reticulon homology domain (RHD), the conserved hydrophobic domain encompassing two short hairpin transmembrane domains. RHD resides in the outer leaflet of the ER membrane, generating high-curvature ER membrane. While most of the membrane proteins destined to enter the secretory pathway are cotranslationally targeted and inserted into ER membrane, the molecular mechanism how the RHD-containing proteins are targeted and inserted into the ER membrane remains to be clarified. Here we show that RHD-containing proteins can be posttranslationally targeted to the ER membrane. PEX19, a cytosolic peroxin, selectively recognizes the nascent RHD-containing proteins and mediates their posttranslational targeting in cooperation with PEX3, a membrane peroxin. Thus, these peroxisome biogenesis factors provide an alternative posttranslational route for membrane insertion of the RHD-containing proteins, implying that ER membrane shaping and peroxisome biogenesis may be coordinated by the posttranslational membrane insertion.