Class I peroxisomal membrane protein import

Stable Identifier
Homo sapiens
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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
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
16280322 In vitro transport of membrane proteins to peroxisomes by shuttling receptor Pex19p

Matsuzono, Y, Fujiki, Y

J. Biol. Chem. 2006
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
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