Membrane topology of the 22 kDa integral peroxisomal membrane protein

Káldi, Krisztina; Diestelkötter, Petra; Stenbeck, Gudrun; Auerbach, Sylvia; Jäkle, Ursula; Mägert, Hans-Jürgen; Wieland, Felix; Just, Wilhelm W.

doi:10.1016/0014-5793(93)81167-x

Cited by 38 publications

(22 citation statements)

References 39 publications

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“…The amino acid sequence of the human PMP22, as shown in Fig. 1, is 77% (44), human (Hs) PMP22, rat (Rn) PMP22 (25), human (Hs) PEX3 (33), and PEX3 of Pichia pastoris (37). Amino acid residues preserved in different peroxisomal membrane proteins are indicated in boldface type.…”

Section: Resultsmentioning

confidence: 99%

Two Different Targeting Signals Direct Human Peroxisomal Membrane Protein 22 to Peroxisomes

Brosius

Dehmel

Gärtner

2002

Journal of Biological Chemistry

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The 22-kDa peroxisomal membrane protein (PMP22) is a major component of peroxisomal membranes in mammals. Although its precise role in peroxisome function is poorly understood, it seems to be involved in pore forming activity and may contribute to the unspecific permeability of the organelle membrane. PMP22 is synthesized on free cytosolic ribosomes and then directed to the peroxisome membrane by specific targeting information. Previous studies in rats revealed that PMP22 contains one distinct peroxisomal membrane targeting signal in the amino-terminal cytoplasmic tail. We cloned and characterized the targeting signal of human PMP22 and compared it with the already described characteristics of the corresponding rat protein. Amino acid sequence alignment of rat and human protein revealed 77% identity including a high conservation of several protein motifs. We expressed various deletion constructs of PMP22 in fusion with the green fluorescent protein in COS-7 cells and determined their intracellular localization. In contrast to previous studies on rat PMP22 and most other peroxisomal membrane proteins, we showed that human as well as rat PMP22 contains two distinct and nonoverlapping peroxisomal membrane targeting signals, one in the amino-terminal and the other in the carboxyl-terminal protein region. They consist of two transmembrane domains and adjacent protein loops with almost identical basic clusters. Both of these peroxisomal targeting regions interact with PEX19, a factor required for peroxisome membrane synthesis. In addition, we observed that fusing the green fluorescent protein immediately adjacent to the targeting region completely abolishes targeting function and mislocalizes PMP22 to the cytosol.

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Section: Resultsmentioning

confidence: 99%

Two Different Targeting Signals Direct Human Peroxisomal Membrane Protein 22 to Peroxisomes

Brosius

Dehmel

Gärtner

2002

Journal of Biological Chemistry

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“…These are the four half ABC transporters (PMP70 (7), PMP70R (23), ALDP (19) and ALDR (24)), Pex14p (25), Pex13p (17), Pex12p (26), Pex11p (9), Pex10p (27), Pex3p (28), Pex2p (29), a peroxisomal Ca 2ϩ -dependent solute carrier (30) PMP34 (31), and PMP22 (8). Unfortunately, a correlation between these known polypeptides and the SDS-PAGE profile of total membrane proteins from mammalian peroxisomes was never performed, the exceptions being PMP70, PMP22 (the two most abundant PMPs), and Pex11p (an abundant protein in clofibrate-treated rats).…”

Section: Polypeptide Composition Of Peroxisomal Membranes From Rat Livermentioning

confidence: 99%

Alkaline Density Gradient Floatation of Membranes: Polypeptide Composition of the Mammalian Peroxisomal Membrane

Gouveia

Reguenga

Oliveira

et al. 1999

Analytical Biochemistry

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“…Recently PMP70 was suggested to be essential for peroxisome formation (21). PMP22 was also cloned and sequenced and it was suggested that the topology of PMP22 was similar to those of Mpv 17 and certain transmitter gated ion channels, although the function of PMP22 has not yet been described (22). Recently peroxisome assembly factor 1, a peroxisomal integral membrane protein with molecular mass of 35 kDa was also cloned and sequenced (23).…”

mentioning

confidence: 99%

Insertion of the 70-kDa Peroxisomal Membrane Protein into Peroxisomal Membranes in Vivo and in Vitro

Imanaka

Shiina

Takano

et al. 1996

Journal of Biological Chemistry

117

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S-PMP70s, with a molecular mass greater than 50 kDa, bound to and inserted into peroxisomal membranes, whereas truncated 35 S-PMP70s smaller than 45 kDa did not. These results suggest that PMP70 is post-translationally transported to peroxisomes without processing and inserted into peroxisomal membranes by a specific mechanism in which a proteinaceous receptor and a certain internal sequence of PMP70 are involved.Peroxisomes are organelles bounded by a single membrane which are present in almost all eukaryotic cells. The peroxisomes are involved in a variety of metabolic processes including peroxide-based respiration, oxidative degradation of purines and fatty acids, and synthesis of plasmalogen and bile acids (1, 2). It has recently been suggested that peroxisomes are formed by post-translational import of newly synthesized proteins into pre-existing peroxisomes, which then divide (3-5). In rat liver, it is known that matrix proteins in peroxisomes are all synthesized on free polysomes in the cytosol. Post-translational import of these proteins into peroxisomes has been shown by in vivo pulse-chase (6, 7) and also by in vitro import experiments (8 -12). We developed an in vitro system based on the import of radiolabeled acyl-CoA oxidase (AOx) 1 into purified rat liver peroxisomes and showed that ATP hydrolysis was required for the translocation of AOx through peroxisomal membranes (9). At least two types of peroxisomal targeting sequences (PTSs) have been found. PTS1 consists of the sequence Ser-Lys-Leu (or closely related) at the carboxyl terminus (10, 13) and PTS2, which in 3-ketoacyl-CoA thiolase is found in the 11 amino acids of the amino-terminal leader sequence (14,15).The membranes of rat liver peroxisomes contain several integral membrane proteins not found in other organelles. Polypeptides of 69/70 and 22 kDa have been identified as major components and polypeptides of 57, 53, 35/36, and 26/27 kDa have been identified as minor components of peroxisomal membranes (16 -19). The 70-kDa peroxisomal membrane protein (PMP70) is markedly induced by administration of hypolipidemic agents and parallels peroxisome proliferation (17, 18). We cloned and sequenced PMP70 and found that PMP70 belonged to a superfamily called an ATP-binding cassette protein, conferring multidrug resistance to tumor cells (20). Recently PMP70 was suggested to be essential for peroxisome formation (21). PMP22 was also cloned and sequenced and it was suggested that the topology of PMP22 was similar to those of Mpv 17 and certain transmitter gated ion channels, although the function of PMP22 has not yet been described (22). Recently peroxisome assembly factor 1, a peroxisomal integral membrane protein with molecular mass of 35 kDa was also cloned and sequenced (23).A number of studies have been carried out to further investigate the biogenesis of peroxisomal membrane proteins (PMPs). We, and other laboratories, have shown that PMP70, -26, and -22 were synthesized on free polysomes (24 -26), suggesting that the PMPs are likely to be insert...

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Membrane topology of the 22 kDa integral peroxisomal membrane protein

Cited by 38 publications

References 39 publications

Two Different Targeting Signals Direct Human Peroxisomal Membrane Protein 22 to Peroxisomes

Two Different Targeting Signals Direct Human Peroxisomal Membrane Protein 22 to Peroxisomes

Alkaline Density Gradient Floatation of Membranes: Polypeptide Composition of the Mammalian Peroxisomal Membrane

Insertion of the 70-kDa Peroxisomal Membrane Protein into Peroxisomal Membranes in Vivo and in Vitro

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