title: Overexpression of a human and a fungal ABC transporter similarly suppresses the differentiation defects of a fungal peroxisomal mutant but introduces pleiotropic cellular effects.
abstract: Among the peroxisome membrane proteins, some are required for peroxisome biogenesis (e.g. PEX2) while others are not, e.g. ABC (ATP-binding cassette) transporters. Unexpectedly, overproduction of the peroxisomal ABC transporter PMP70 was found to be able to restore peroxisome biogenesis in mammalian pex2 mutant cell lines. In the filamentous fungus Podospora anserina, pex2 mutations not only impair peroxisome biogenesis but also cause a precise cell differentiation defect. Here, we show that both defects are partially suppressed by expression of the human cDNA encoding PMP70. In addition, PMP70 expression causes new developmental defects, different from those induced by pex2 mutations. We also show that overexpression of the P. anserina pABC1 gene, which encodes a peroxisomal ABC transporter, leads to similar effects. Taken together, our results demonstrate that: (i) the genetic relationship between PEX2 and PMP70, initially observed in mammals, has been conserved through evolution; (ii) the cell differentiation defect observed in the P. anserina pex2 mutants is indeed linked to impairment in peroxisome biogenesis; and (iii) unexpected detrimental cellular defects result from overproduction of peroxisomal ABC transporters.
authors.affiliation: Institut de Génétique et Microbiologie, UMR 8621, Bat. 400, Université Paris-Sud, 91405 Orsay cedex, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Boisnard
authors.forename: Denise
authors.initials: D
authors.lastname: Zickler
authors.forename: Marguerite
authors.initials: M
authors.lastname: Picard
authors.forename: Véronique
authors.initials: V
authors.lastname: Berteaux-Lecellier
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D005075:Biological Evolution; D018076:DNA, Complementary; D015870:Gene Expression; D005800:Genes, Fungal; D005816:Genetic Complementation Test; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D009024:Morphogenesis; D009154:Mutation; D000074428:Peroxisomal Biogenesis Factor 2; D020675:Peroxisomes / Q000378:metabolism* / Q000648:ultrastructure; D010641:Phenotype; D011994:Recombinant Proteins / Q000378:metabolism; D020037:Sordariales / Q000166:cytology* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D013489:Suppression, Genetic
chemical_list: C063305:ABCD3 protein, human; D018528:ATP-Binding Cassette Transporters; D018076:DNA, Complementary; D008565:Membrane Proteins; C000614230:PEX2 protein, human; D011994:Recombinant Proteins; D000074428:Peroxisomal Biogenesis Factor 2