Predicting the function and subcellular location of Caenorhabditis elegansproteins similar to Saccharomyces cerevisiae beta-oxidation enzymes

The role of peroxisomal processes in the maintenance of neurons has not bee n thoroughly investigated. We propose using Caenorhabditis elegans as a mod el organism for studying the molecular basis underlying neurodegeneration i n certain human peroxisomal disorders, e.g. Zellweger syndrome, since the n ematode neural network is well characterized and relatively simple in funct ion. Here we have identified C. elegans PEX-5 (C34C6.6) representing the re ceptor for peroxisomal targeting signal type I (PTSI), defective in patient s with such disorders. PEX-5 interacted strongly in a two-hybrid assay with Gal4p-SKL, and a screen using PEX-5 identified interaction partners that w ere predominantly terminated with PTS1 or its variants. A list of C. elegan s proteins with similarities to well-characterized yeast P-oxidation enzyme s was compiled by homology probing. The possible subcellular localization o f these orthologues was predicted using an algorithm based on trafficking s ignals. Examining the C termini of selected nematode proteins for PTS1 func tion substantiated predictions made regarding the proteins' peroxisomal loc ation. It is concluded that the eukaryotic PEX5-dependent route for importi ng PTS1-containing proteins into peroxisomes is conserved in nematodes, C, elegans might emerge as an attractive model system for studying the importa nce of peroxisomes and affiliated processes in neurodegeneration, and also for studying a P-oxidation process that is potentially compartmentalized in both mitochondria and peroxisomes, Copyright (C) 2000 John Wiley & Sons, L td.