Human adrenoleukodystrophy protein and related peroxisomal ABC transporters interact with the peroxisomal assembly protein PEX19p

Four ABC half transporters (ALDP, ALDRP, PMP70, and PMP69) have been identi fied in the mammalian peroxisomal membrane but no function has been unambig uously assigned to any of them. To date X-linked adrenoleukodystrophy (X-AL D) 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 pub-down assays, we identified the peroxin PEX19p as a novel interactor of ALDP, ALDRP, and PMP70. The cytosolic farnesylated protein PEX19p was previ ously shown to be involved in an early step of the peroxisomal biogenesis. The PEX19p interaction occurs in an internal N-terminal region of ALDP whic h we verified to be important for proper peroxisomal targeting of this prot ein. Farnesylated wild-type PEX19p and a farnesylation-deficient mutant PEX 19p did not differ in their ability to bind to ALDP. Our data provide evide nce that PEX19p is a cytosolic acceptor protein for the peroxisomal ABC tra nsporters ALDP, PMP70, and ALDRP and might be involved in the intracellular sorting and trafficking of these proteins to the peroxisomal membrane. (C) 2000 Academic Press.