title: Human adrenoleukodystrophy protein and related peroxisomal ABC transporters interact with the peroxisomal assembly protein PEX19p.
abstract: Four ABC half transporters (ALDP, ALDRP, PMP70, and PMP69) have been identified in the mammalian peroxisomal membrane but no function has been unambiguously assigned to any of them. To date X-linked adrenoleukodystrophy (X-ALD) is the only human disease known to result from a defect of one of these ABC transporters, ALDP. Using the yeast two-hybrid system and in vitro GST pull-down assays, we identified the peroxin PEX19p as a novel interactor of ALDP, ALDRP, and PMP70. The cytosolic farnesylated protein PEX19p was previously shown to be involved in an early step of the peroxisomal biogenesis. The PEX19p interaction occurs in an internal N-terminal region of ALDP which we verified to be important for proper peroxisomal targeting of this protein. Farnesylated wild-type PEX19p and a farnesylation-deficient mutant PEX19p did not differ in their ability to bind to ALDP. Our data provide evidence that PEX19p is a cytosolic acceptor protein for the peroxisomal ABC transporters ALDP, PMP70, and ALDRP and might be involved in the intracellular sorting and trafficking of these proteins to the peroxisomal membrane.
authors.affiliation: GSF-National Research Center for Environment and Health, Institute of Mammalian Genetics, Ingolstaedter Landstrasse 1, Neuherberg, 85764, Germany.
authors.forename: C J
authors.initials: CJ
authors.lastname: Gloeckner
authors.forename: P U
authors.initials: PU
authors.lastname: Mayerhofer
authors.forename: P
authors.initials: P
authors.lastname: Landgraf
authors.forename: A C
authors.initials: AC
authors.lastname: Muntau
authors.forename: A
authors.initials: A
authors.lastname: Holzinger
authors.forename: J K
authors.initials: JK
authors.lastname: Gerber
authors.forename: S
authors.initials: S
authors.lastname: Kammerer
authors.forename: J
authors.initials: J
authors.lastname: Adamski
authors.forename: A A
authors.initials: AA
authors.lastname: Roscher
mesh_terms: D000074061:ATP Binding Cassette Transporter, Subfamily D; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000378:metabolism*; D000326:Adrenoleukodystrophy / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D018076:DNA, Complementary / Q000378:metabolism; D015723:Gene Library; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D020675:Peroxisomes / Q000737:chemistry / Q000378:metabolism*; D010957:Plasmids; D011485:Protein Binding; D017368:Protein Prenylation; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D020798:Two-Hybrid System Techniques
chemical_list: C115572:ABCD1 protein, human; C431694:ABCD2 protein, human; C063305:ABCD3 protein, human; D000074061:ATP Binding Cassette Transporter, Subfamily D; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters; D018076:DNA, Complementary; D008565:Membrane Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase