Dual function of Sec16B: Endoplasmic reticulum-derived protein secretion and peroxisome biogenesis in mammalian cells

Abstract

The origin of peroxisomes has long been disputed. However, recent evidence suggests that peroxisomes can be formed de novo from the endoplasmic reticulum (ER) in yeast and higher eukaryotes. Sec16A and Sec16B, mammalian orthologs of yeast Sec16, are scaffold proteins that organize ER exit sites by interacting with COPII components. We recently demonstrated that Sec16B, but not Sec16A, regulates the transport of peroxisomal biogenesis factors from the ER to peroxisomes in mammalian cells. The C-terminal region of Sec16B, which is not conserved in Sec16A, is required for this function. The data suggest that Sec16B in ER areas other than ER exit sites plays this role. Our findings provide an unexpected connection between at least part of the COPII machinery and the formation of preperoxisomal vesicles at the ER, and offer an explanation of how secretory and peroxisomal trafficking from the ER are distinguished.

Figure 1

Model of the role of Sec16B in the formation of membrane carriers destined for peroxisomes. As in the case of Sec16 in ER exit sites, Sec16B may interact with vesicle coat components that facilitate the deformation of ER membranes, and the incorporation of PMPs such as Pex16 and Pex3 into nascent vesicles. Alternatively, Sec16B may function as a scaffold that interacts directly or indirectly with PMPs and putative fission factors on ER membranes. In the absence of Sec16B, Pex3 seems to be degraded by the ubiquitin-proteasome system. In yeast, transport carriers are detached from ER membranes at budding sites,, but in mammalian cells, pre-peroxisomal structures (subdomains in the smooth ER) may be associated with the peroxisomal reticulum.