Functional heterogeneity of C-terminal peroxisome targeting signal 1 in PEX5-defective patients.

[neonatal adrenoleukodystrophy]

To investigate mechanisms related to functions of the peroxisome targeting signal (PTS ) 1 receptor , Pex 5 p , we analyzed peroxisome matrix protein import in fibroblasts from three patients with peroxisome biogenesis disorders , all with different mutations in the PEX 5 gene . The patients 2 -01 (Zellweger syndrome ) and 2 -05 (neonatal adrenoleukodystrophy ) have the reported mutations , R 390 X and N 489 K , and patient 2 -03 (infantile Refsum disease ) has a newly identified mutation , S 563 W . Fibroblasts from 2 -03 (S 563 W ) were detected in both PTS 1 and PTS 2 imports despite the PEX 5 defect , findings in contrast with fibroblasts from 2 -05 (N 489 K ) severely defective in PTS 1 import and those from 2 -01 (R 390 X ) severely defective in both PTS 1 and PTS 2 . The PTS 1 receptor in 2 -03 is functional for only the C-terminal -SKL sequence (acyl-CoA oxidase ) and had little or no function for C-terminal -AKL (D-bifunctional protein and sterol carrier protein 2 ) and -KANL (catalase ) sequences , respectively . After transfection of these mutated PEX 5 cDNA into the PEX 5 -defective CHO mutant , transformants of ZP 1 02 revealed that each mutation was responsible for each dysfunction of the PTS 1 import . It seems apparent that -AKL and -KANL are poorer variants of PTS 1 and are likely to be more susceptible to effects of mutation of its receptor , Pex 5 p .

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Diseases presenting "findings in contrast with fibroblasts from 2" symptom

neonatal adrenoleukodystrophy

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