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

C J Gloeckner1, P U Mayerhofer, P Landgraf

  • 1GSF-National Research Center for Environment and Health, Institute of Mammalian Genetics, Ingolstaedter Landstrasse 1, Neuherberg, 85764, Germany.

Insights

The peroxin PEX19p interacts with peroxisomal ABC transporters ALDP, ALDRP, and PMP70. This interaction is crucial for the sorting and trafficking of these transporters to the peroxisomal membrane.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mammalian peroxisomal membranes contain four identified ABC half transporters: ALDP, ALDRP, PMP70, and PMP69.
  • X-linked adrenoleukodystrophy (X-ALD) is the sole human disease linked to a defect in the ABC transporter ALDP.
  • The peroxin PEX19p is a cytosolic, farnesylated protein previously implicated in peroxisomal biogenesis.

Purpose of the Study:

  • To identify novel interactors of peroxisomal ABC transporters.
  • To elucidate the role of PEX19p in the function and localization of peroxisomal ABC transporters.

Main Methods:

  • Yeast two-hybrid system screening.
  • In vitro GST pull-down assays.
  • Analysis of protein-protein interactions and peroxisomal targeting.

Main Results:

  • PEX19p was identified as a novel interactor of ALDP, ALDRP, and PMP70.
  • The interaction site on ALDP was mapped to an N-terminal region critical for peroxisomal targeting.
  • Farnesylation status of PEX19p did not affect its binding affinity to ALDP.

Conclusions:

  • PEX19p acts as a cytosolic acceptor protein for peroxisomal ABC transporters ALDP, PMP70, and ALDRP.
  • PEX19p likely plays a role in the intracellular sorting and trafficking of these transporters to the peroxisomal membrane.

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