Peroxisomal Membrane Proteins Insert into the Endoplasmic Reticulum

Abstract

We demonstrate that the entry of peroxisomal membrane proteins (PMPs) into the ER is mediated by the general ER import machinery. Within the ER, PMPs attain their correct topology and subsequently travel to peroxisomes. Our results show that the ER forms an obligate requirement to maintain peroxisomes in multiplying cells.

Peroxisomal Biogenesis: Genetic Disorders Reveal the Mechanisms

“…Also in yeast, recombinant Pex3p bearing an attached signal sequence and, therefore, unequivocally addressed to the ER, ends up integrated into peroxisomes (22). More recently, work on Saccaromyces reported ER targeting of 16 PMPs mediated by Sec61p and Get13, both in proliferating wild-type cells and in mutant cells lacking peroxisomes (48). This work also showed that PMPs leave the ER in a Pex3-Pex19p-dependent manner, implying a new functional role for Pex3p and Pex19p, i.e.…”

“…An early study in rat liver using cell fractionation methods described data suggesting the presence of PMP50 and PMP36 in ER membrane fractions (51). Only very recently a targeting of a variety of PMPs to the ER has been reported in yeast (48). However, this is a previously unknown feature of ZS cells, which not only entails great interest regarding the role of the ER in peroxisomal biogenesis but also suggests a new role of Pex3p and Pex16p dealing with the traffic of PMPs from the ER to peroxisomes.…”

“…Previous studies in mammalian cells lacking Pex19p have shown that exogenously expressed Pex16p-GFP is targeted to the ER and accumulates there without promoting newly synthesis of peroxisomes (30). There are also studies in yeast lacking Pex3p or Pex19p that show PMPs arrested in the ER (48), and more recently, that Pex19p is part of the mechanism which produces membrane carriers containing Pex3p from the ER (49). Taken together with our results, the overall evidence indicates that Pex16p does not require Pex3p for its insertion into the ER membrane, in agreement with its previously reported cotranslational incorporation (30), but seemingly does require Pex3p and Pex19p for exiting the ER in peroxisomal membrane precursors.…”

Clearing tail-anchored proteins from mitochondria

“…(B) In cells with a defective GET pathway, Pex15 is mistargeted to the mitochondrial outer membrane and is removed from this compartment with the aid of the AAA-ATPase Msp1 (red arrows). Small amounts of Pex15 can be correctly delivered to peroxisomes (12), possibly by the alternative Pex19/Pex3 pathway.…”

“…1A). The peroxin Pex15 is initially inserted into the ER via the GET pathway and then transferred to peroxisomes via vesicular transport (8,12,13). Other tailanchored proteins use an ER-independent pathway, where the precursors are targeted to peroxisomes via the Pex19 cytosolic chaperone and the peroxisome-resident receptor Pex3 (14).…”