Reactome | Class I peroxisomal membrane protein import

Class I peroxisomal membrane protein import

Stable Identifier

R-HSA-9603798

DOI

10.3180/R-HSA-9603798.1

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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Class I peroxisomal membrane protein import

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Most peroxisomal membrane proteins (PMPs) are inserted into the peroxisomal membrane by the receptor-chaperone PEX19 and the docking receptor PEX3 (Soukupova et al. 1999, Muntau et al. 2003, Fang et al. 2004, Fujiki et al. 2006, Matsuzono and Fujiki 2006, Matsuzono et al. 2006, Pinto et al. 2006, Sato et al. 2008, Sato et al. 2010, Schmidt et al. 2010, Hattula et al. 2014, reviewed in Fujiki et al. 2014, Mayerhofer 2016). PEX19 binds the PMP as it is translated in the cytosol. Recognition of the PMP by PEX 19 appears to depend on positively charged residues in the transmembrane domain of the PMP (Costello et al. 2017). The PEX19:PMP complex then interacts with PEX3 located in the peroxisomal membrane. Through a mechanism that is not yet clear, the PMP is inserted into the peroxisomal membrane and PEX19 dissociates from PEX3. A current model involves transfer of the PMP from PEX19 to a hydrophobic region of PEX3 followed by insertion of the PMP into the membrane (Chen et al. 2014, reviewed by Giannopoulou et al. 2016). The process does not appear to require hydrolysis of ATP or GTP (Pinto et al. 2006).
Unlike other PMPs, PEX3 is inserted into the peroxisomal membrane by binding PEX19 and then docking with PEX16 (Matsuzaki and Fujiki 2008). Both PEX3 and PEX16 can also be co-translationally inserted into the endoplasmic reticulum membrane (Kim et al. 2006, Yonekawa et al. 2011, Aranovich et al. 2014, Hua et al. 2015, Mayerhofer et al. 2016). This region of the ER membrane then buds to contribute to new peroxisomes. PEX3 is also observed to insert into the mitochondrial outer membrane (Sugiura et al. 2017). Regions of the ER membrane and mitochondrial outer membrane are then released to form pre-peroxisomal vesicles which fuse to form new peroxisomes (Sugiura et al. 2017). Peroxisomes therefore appear to arise from fission of existing peroxisomes and production of new peroxisomes from precursors derived from mitochondria and the ER (Sugiura et al. 2017, reviewed in Fujiki et al. 2014, Hua and Kim 2016).

Literature References

PubMed ID	Title	Journal	Year
16280322	In vitro transport of membrane proteins to peroxisomes by shuttling receptor Pex19p Matsuzono, Y, Fujiki, Y	J. Biol. Chem.	2006
21102411	Structural basis for docking of peroxisomal membrane protein carrier Pex19p onto its receptor Pex3p Sato, Y, Shibata, H, Nakatsu, T, Nakano, H, Kashiwayama, Y, Imanaka, T, Kato, H	EMBO J.	2010
16717127	The origin and maintenance of mammalian peroxisomes involves a de novo PEX16-dependent pathway from the ER Kim, PK, Mullen, RT, Schumann, U, Lippincott-Schwartz, J	J. Cell Biol.	2006
20554521	Insights into peroxisome function from the structure of PEX3 in complex with a soluble fragment of PEX19 Schmidt, F, Treiber, N, Zocher, G, Bjelic, S, Steinmetz, MO, Kalbacher, H, Stehle, T, Dodt, G	J. Biol. Chem.	2010
10430017	Identification and characterization of the human peroxin PEX3 Soukupova, M, Sprenger, C, Gorgas, K, Kunau, WH, Dodt, G	Eur. J. Cell Biol.	1999
25062251	Association between the intrinsically disordered protein PEX19 and PEX3 Hattula, K, Hirschberg, D, Kalkkinen, N, Butcher, SJ, Ora, A	PLoS ONE	2014
25517356	Hydrophobic handoff for direct delivery of peroxisome tail-anchored proteins Chen, Y, Pieuchot, L, Loh, RA, Yang, J, Kari, TM, Wong, JY, Jedd, G	Nat Commun	2014
17069900	Import of peroxisomal membrane proteins: the interplay of Pex3p- and Pex19p-mediated interactions Fujiki, Y, Matsuzono, Y, Matsuzaki, T, Fransen, M	Biochim. Biophys. Acta	2006
15007061	PEX3 functions as a PEX19 docking factor in the import of class I peroxisomal membrane proteins Fang, Y, Morrell, JC, Jones, JM, Gould, SJ	J Cell Biol	2004
16895967	Functional domain mapping of peroxin Pex19p: interaction with Pex3p is essential for function and translocation Matsuzono, Y, Matsuzaki, T, Fujiki, Y	J. Cell. Sci.	2006
28325759	Predicting the targeting of tail-anchored proteins to subcellular compartments in mammalian cells Costello, JL, Castro, IG, Camões, F, Schrader, TA, McNeall, D, Yang, J, Giannopoulou, EA, Gomes, S, Pogenberg, V, Bonekamp, NA, Ribeiro, D, Wilmanns, M, Jedd, G, Islinger, M, Schrader, M	J. Cell. Sci.	2017
25903784	Multiple Domains in PEX16 Mediate Its Trafficking and Recruitment of Peroxisomal Proteins to the ER Hua, R, Gidda, SK, Aranovich, A, Mullen, RT, Kim, PK	Traffic	2015
26434995	Towards the molecular mechanism of the integration of peroxisomal membrane proteins Giannopoulou, EA, Emmanouilidis, L, Sattler, M, Dodt, G, Wilmanns, M	Biochim. Biophys. Acta	2016
25177298	Peroxisome biogenesis in mammalian cells Fujiki, Y, Okumoto, K, Mukai, S, Honsho, M, Tamura, S	Front Physiol	2014
12924628	The interaction between human PEX3 and PEX19 characterized by fluorescence resonance energy transfer (FRET) analysis Muntau, AC, Roscher, AA, Kunau, WH, Dodt, G	Eur. J. Cell Biol.	2003
16980692	The import competence of a peroxisomal membrane protein is determined by Pex19p before the docking step Pinto, MP, Grou, CP, Alencastre, IS, Oliveira, ME, Sá-Miranda, C, Fransen, M, Azevedo, JE	J. Biol. Chem.	2006
25002403	PEX16 contributes to peroxisome maintenance by constantly trafficking PEX3 via the ER Aranovich, A, Hua, R, Rutenberg, AD, Kim, PK	J. Cell. Sci.	2014
28146471	Newly born peroxisomes are a hybrid of mitochondrial and ER-derived pre-peroxisomes Sugiura, A, Mattie, S, Prudent, J, McBride, HM	Nature	2017
21768384	Sec16B is involved in the endoplasmic reticulum export of the peroxisomal membrane biogenesis factor peroxin 16 (Pex16) in mammalian cells Yonekawa, S, Furuno, A, Baba, T, Fujiki, Y, Ogasawara, Y, Yamamoto, A, Tagaya, M, Tani, K	Proc. Natl. Acad. Sci. U.S.A.	2011
18174172	Characterization of the interaction between recombinant human peroxin Pex3p and Pex19p: identification of TRP-104 IN Pex3p as a critical residue for the interaction Sato, Y, Shibata, H, Nakano, H, Matsuzono, Y, Kashiwayama, Y, Kobayashi, Y, Fujiki, Y, Imanaka, T, Kato, H	J. Biol. Chem.	2008
26408931	Multiple paths to peroxisomes: Mechanism of peroxisome maintenance in mammals Hua, R, Kim, PK	Biochim. Biophys. Acta	2016
26392202	Targeting and insertion of peroxisomal membrane proteins: ER trafficking versus direct delivery to peroxisomes Mayerhofer, PU	Biochim. Biophys. Acta	2016
19114594	The peroxisomal membrane protein import receptor Pex3p is directly transported to peroxisomes by a novel Pex19p- and Pex16p-dependent pathway Matsuzaki, T, Fujiki, Y	J. Cell Biol.	2008
26572236	Human Peroxin PEX3 Is Co-translationally Integrated into the ER and Exits the ER in Budding Vesicles Mayerhofer, PU, Bañó-Polo, M, Mingarro, I, Johnson, AE	Traffic	2016