Pex3p Initiates the Formation of a Preperoxisomal Compartment from a Subdomain of the Endoplasmic Reticulum in Saccharomyces cerevisiae

Tam, Yun K.; Fagarasanu, Andrei; Fagarasanu, Monica; Rachubinski, Richard A.

doi:10.1074/jbc.m506208200

Cited by 151 publications

(197 citation statements)

References 38 publications

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“…Similarly, and consistent with published work (22), peroxisomal targeting of Pex3p was observed for the full-length protein (Fig. 1E) and its N-terminal 45 amino acids (Fig.…”

Section: Topology and Targeting Signals Are Similar For Scpex3psupporting

confidence: 79%

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The N-domain of Pex22p Can Functionally Replace the Pex3p N-domain in Targeting and Peroxisome Formation

Halbach

Rucktäschel

Rottensteiner

et al. 2009

Journal of Biological Chemistry

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Pex3p is a central component of the import machinery for peroxisomal membrane proteins (PMPs) that can reach peroxisomes via the endoplasmic reticulum (ER) and even trigger de novo peroxisome formation from the ER. Pex19p is the import receptor for type I PMPs, whereas targeting of type II PMPs, of which Pex3p so far represents the only species, does not require Pex19p. Pex3p possesses two domains with distinct function: a short N-terminal domain, which harbors the information for peroxisomal (and ER) targeting, and a C-terminal domain, which faces the cytosol and serves as a docking site for Pex19p, thereby delivering newly synthesized PMPs to the peroxisome. Here we show that the N-terminal domain of Pex3p can be functionally replaced by the N-terminal peroxisomal membrane targeting signal (mPTS) of Pex22p, a supposedly unrelated component of the import machinery for peroxisomal matrix proteins. An exchange of the mPTS of Pex22p by that of Pex3p likewise fully preserved the function of Pex22p. Neither of the two mPTS interacted with Pex19p, and in the absence of Pex19p, colocalization of Pex3p and Pex22p was observed, indicating that also Pex22p is targeted to peroxisomes by a type II mPTS. When a type I mPTS was hooked to the C-terminal domains of Pex22p and Pex3p, function was retained in the case of Pex22p and in part even for Pex3p. The C-terminal domain of Pex3p thus contains the relevant information required for de novo peroxisome formation, thereby challenging the concept of the N terminus of Pex3p being key in that process.Peroxisome biogenesis requires a set of proteins called peroxins, most of which accomplish the faithful import of matrix proteins (1-3). Two types of targeting signals are known to direct proteins to the peroxisomal lumen: a C-terminal peroxisomal targeting signal type 1 (PTS1) 2 comprising the C-terminal tripeptide SKL and conservative variants thereof, and an N-terminal PTS2. The import of peroxisomal membrane proteins (PMPs) follows a distinct route and depends on Pex3p and Pex19p in all of the species analyzed (4) and on Pex16p in mammals (5, 6).The majority of PMPs are recognized by Pex19p during or early after synthesis in the cytosol. Pex19p binding not only protects these hydrophobic proteins from aggregation but also delivers them to the peroxisomal membrane (7-10). Docking of the cargo-loaded Pex19p receptor at the peroxisomal membrane occurs via the C-terminal cytoplasmic domain of Pex3p (10 -13). In a subsequent, poorly understood step, PMPs are released from Pex19p for insertion into the peroxisomal membrane. Although some controversy exists in the literature on the nature of a peroxisomal membrane protein targeting signal (mPTS), it requires one or more transmembrane spans and a targeting-specific sequence that is identical to the Pex19p-binding site in at least a subset of PMPs (4, 10, 11).In mutants with a specific block in matrix protein import, PMPs are normally imported into so-called peroxisomal remnants. In contrast, in the absence of the peroxins required for PM...

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“…Similarly, and consistent with published work (22), peroxisomal targeting of Pex3p was observed for the full-length protein (Fig. 1E) and its N-terminal 45 amino acids (Fig.…”

Section: Topology and Targeting Signals Are Similar For Scpex3psupporting

confidence: 79%

“…Consent exists on Pex3p being essential for PMP import, and it is widely considered as an early peroxin that is able to trigger de novo peroxisome formation by virtue of its N-terminal mPTS, which comprises ϳ45 amino acids (22)(23)(24). In mammals targeting of Pex3p turned out to be Pex19p-independent, whereas all other PMPs tested did require Pex19p (10).…”

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confidence: 99%

The N-domain of Pex22p Can Functionally Replace the Pex3p N-domain in Targeting and Peroxisome Formation

Halbach

Rucktäschel

Rottensteiner

et al. 2009

Journal of Biological Chemistry

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“…Peroxisomes are unique amongst cell organelles as they can arise de novo from the ER (endoplasmic reticulum) (Hoepfner et al, 2005;Tam et al, 2005;Kim et al, 2006), but mature or even change their function by the import of proteins across their boundary membranes. As well as arising from the ER, peroxisomes can proliferate, divide and be partitioned between daughter cells during division (Motley and Hettema, 2007;Fagarasanu et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Getting a camel through the eye of a needle: the import of folded proteins by peroxisomes

Lanyon‐Hogg

Warriner

Baker

2010

Biology of the Cell

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Peroxisomes are a family of organelles which have many unusual features. They can arise de novo from the endoplasmic reticulum by a still poorly characterized process, yet possess a unique machinery for the import of their matrix proteins. As peroxisomes lack DNA, their function, which is highly variable and dependent on developmental and/or environmental conditions, is determined by the post-translational import of specific metabolic enzymes in folded or oligomeric states. The two classes of matrix targeting signals for peroxisomal proteins [PTS1 (peroxisomal targeting signal 1) and PTS2] are recognized by cytosolic receptors [PEX5 (peroxin 5) and PEX7 respectively] which escort their cargo proteins to, or possibly across, the peroxisome membrane. Although the membrane translocation mechanism remains unclear, it appears to be driven by thermodynamically favourable binding interactions. Recycling of the receptors from the peroxisome membrane requires ATP hydrolysis for two linked processes: ubiquitination of PEX5 (and the PEX7 co-receptors in yeast) and the function of two peroxisome-associated AAA (ATPase associated with various cellular activities) ATPases, which play a role in recycling or turnover of the ubiquitinated receptors. This review summarizes and integrates recent findings on peroxisome matrix protein import from yeast, plant and mammalian model systems, and discusses some of the gaps in our understanding of this remarkable protein transport system.

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“…Although a limited number of PMPs first target the endoplasmic reticulum and then traffic to peroxisomes (7)(8)(9)(10)(11), most PMPs are inserted into the peroxisomal membrane directly from the cytosol (12)(13)(14)(15)(16). The direct insertion of PMPs into the peroxisomal membrane is facilitated by Pex19p, a peroxin that is localized predominantly to the cytosol and to a much lesser extent at the surface of peroxisomes (17)(18)(19).…”

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confidence: 99%

Pex19p Binds Pex30p and Pex32p at Regions Required for Their Peroxisomal Localization but Separate from Their Peroxisomal Targeting Signals

Vizeacoumar

Vreden

Aitchison

et al. 2006

Journal of Biological Chemistry

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The assembly of proteins in the peroxisomal membrane is a multistep process requiring their recognition in the cytosol, targeting to and insertion into the peroxisomal membrane, and stabilization within the lipid bilayer. The peroxin Pex19p has been proposed to be either the receptor that recognizes and targets newly synthesized peroxisomal membrane proteins (PMP) to the peroxisome or a chaperone required for stabilization of PMPs at the peroxisomal membrane. Differentiating between these two roles for The synthesis of nuclear-encoded proteins begins in the cytosol. A protein that is destined for an organelle is directed from the cytosol to the organelle by a sequence or sequences within the protein that contain information essential for targeting the protein to the organelle. These sequences are recognized by receptors in the cytosol or at the target membrane. Having arrived at its specific organelle, the protein is then either translocated across the organelle membrane or inserted into the membrane lipid bilayer.Peroxisomes are ubiquitous organelles that perform a variety of essential biochemical functions, notably in fatty acid metabolism. Mature peroxisomes usually appear as spherical structures in electron micrographs, with diameters of 0.5-1.0 m, and surrounded by a single membrane.

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Pex3p Initiates the Formation of a Preperoxisomal Compartment from a Subdomain of the Endoplasmic Reticulum in Saccharomyces cerevisiae

Cited by 151 publications

References 38 publications

The N-domain of Pex22p Can Functionally Replace the Pex3p N-domain in Targeting and Peroxisome Formation

The N-domain of Pex22p Can Functionally Replace the Pex3p N-domain in Targeting and Peroxisome Formation

Getting a camel through the eye of a needle: the import of folded proteins by peroxisomes

Pex19p Binds Pex30p and Pex32p at Regions Required for Their Peroxisomal Localization but Separate from Their Peroxisomal Targeting Signals

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