Rab proteins form in vivo complexes with two isoforms of the GDP-dissociation inhibitor protein (GDI).
GTPases of the Rab family play a key role in the regulation of vesicular transport in eukaryotic cells. Several accessory proteins that regulate their GDP/GTP cycle as well as their subcellular localization have been identified within the past few years. The best known is Rab3A GDP dissociation inhibitor protein (GDI), originally identified as an inhibitor of GDP dissociation from Rab3A, a Rab protein specifically expressed in neuronal and neuroendocrine cells. Recent studies have pointed out a role of Rab3A GDI as a chaperone of several Rab proteins during their cycling between cytosol and membranes and Rab3A GDI has been considered so far as a general regulator of Rab function. However, cDNAs encoding potential isoforms of this protein, called GDI beta and GDI-2, have been recently isolated. In this study, we have characterized cytosolic Rab protein complexes in various cell types and tissues using Mono Q chromatography. We show that in rat brain and in insulin-secreting RINm5F cells, the majority of Rab proteins are complexed with Rab3A GDI. In contrast, in Chinese hamster ovary cells, they are mainly complexed to a protein that we have identified as GDI beta. In rat liver cytosol, Rab proteins form complexes with both isoforms. We also show that the proportion of Rab proteins complexed with either isoform depends on the relative abundance of Rab3A GDI and GDI beta in the cytosol. These findings suggest that GDI isoforms are either redundant or could be involved in the fine control of Rab function.
Yang
C
C
Unité de Génétique Somatique (URA CNRS 361), Institut Pasteur, Paris, France.
Slepnev
V I
VI
Goud
B
B
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain; D016466:CHO Cells; D006224:Cricetinae; D003600:Cytosol / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020730:Guanine Nucleotide Dissociation Inhibitors; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000276:immunology / Q000378:metabolism; D051381:Rats
C086796:GDP dissociation inhibitor 1; D020730:Guanine Nucleotide Dissociation Inhibitors; D046911:Macromolecular Substances; D010455:Peptides; D016271:Proto-Oncogene Proteins c-myc; D019204:GTP-Binding Proteins