Small G proteins in peroxisome biogenesis: the potential involvement of ADP-ribosylation factor 6.
BACKGROUND
Peroxisomes execute diverse and vital functions in virtually every eukaryote. New peroxisomes form by budding from pre-existing organelles or de novo by vesiculation of the ER. It has been suggested that ADP-ribosylation factors and COPI coatomer complexes are involved in these processes.


RESULTS
Here we show that all viable Saccharomyces cerevisiae strains deficient in one of the small GTPases which have an important role in the regulation of vesicular transport contain functional peroxisomes, and that the number of these organelles in oleate-grown cells is significantly upregulated in the arf1 and arf3 null strains compared to the wild-type strain. In addition, we provide evidence that a portion of endogenous Arf6, the mammalian orthologue of yeast Arf3, is associated with the cytoplasmic face of rat liver peroxisomes. Despite this, ablation of Arf6 did neither influence the regulation of peroxisome abundance nor affect the localization of peroxisomal proteins in cultured fetal hepatocytes. However, co-overexpression of wild-type, GTP hydrolysis-defective or (dominant-negative) GTP binding-defective forms of Arf1 and Arf6 caused mislocalization of newly-synthesized peroxisomal proteins and resulted in an alteration of peroxisome morphology.


CONCLUSIONS
These observations suggest that Arf6 is a key player in mammalian peroxisome biogenesis. In addition, they also lend strong support to and extend the concept that specific Arf isoform pairs may act in tandem to regulate exclusive trafficking pathways.
Anthonio
Erin A
EA
Department of Molecular Cell Biology, Catholic University of Leuven, Leuven, Belgium. erin.anthonio@med.kuleuven.be
Brees
Chantal
C
Baumgart-Vogt
Eveline
E
Hongu
Tsunaki
T
Huybrechts
Sofie J
SJ
Van Dijck
Patrick
P
Mannaerts
Guy P
GP
Kanaho
Yasunori
Y
Van Veldhoven
Paul P
PP
Fransen
Marc
M
D020823:ADP-Ribosylation Factor 1 / Q000172:deficiency / Q000378:metabolism; D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000172:deficiency / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D022781:Hepatocytes / Q000201:enzymology; D006801:Humans; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016253:Microscopy, Immunoelectron; D009154:Mutation; D019301:Oleic Acid / Q000378:metabolism; D020675:Peroxisomes / Q000378:metabolism* / Q000648:ultrastructure; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
D000089982:ADP-Ribosylation Factor 6; D029701:Saccharomyces cerevisiae Proteins; D019301:Oleic Acid; C492128:ARF3 protein, S cerevisiae; D020823:ADP-Ribosylation Factor 1; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human; C000715727:Arf6 protein, mouse; C000715349:Arf6 protein, rat
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