Comparative Analysis of Rab GTPases and SNAREs in Eukaryotic Genomes

Abstract

The intracellular vesicular transport is indispensable function for eukaryotic cells to maintain the intracellular membrane compartments. In order that the transport vesicles fuse only to the precise target membranes and that the macromolecules are selectively delivered, unique mutual recognitions are required between the vesicles and the membranes. These unique recognitions and membrane fusions are mediated by the SNARE (Soluble N-ethyl maleimide sensitive factor Attachment protein REceptor) superfamily proteins, which are well conserved throughout the eukaryotic evolution. Recently ongoing eukaryotic genome projects have revealed a number of SNARE molecules in the whole genomes, but the number was fewer than expected suggesting that the same SNARE molecules mediate different transport pathways. For example, sec22p of S.cerevisiae carries both directions of transport between the endoplasmic reticulum (ER) and cis-Golgi apparatus. Therefore, additional proteins should be involved in the roles of mediating unique recognitions. Rab proteins belong to the Ras small GTPase superfamily, and have been considered to be involved in the vesicular transport since the identification of the first Rab molecule in 1983. In 1999, mammalian Rab5, whose localization is early endosomes, was revealed to bind to the tethering factor EEA1 (Early Endosome Antigen 1), which is required before the SNARE mutual recognition, and also binds to Syntaxin6 and 13, t-SNAREs on early endosome. Therefore, SNARE systems and Rab GTPases are considered to be functionally related. For example, the localizations of both of mammalian Rab1 and Rab2 are between ER and cis-Golgi apparatus, while Rab1 mediates the transport from ER to Golgi and Rab2 mediates from Golgi to ER. Thus, it is probable that Rab molecules mediate the vesicular transport processes cooperating with the SNARE system. We formerly performed a hierarchical cluster analysis of SNARE molecules, and showed that SNAREs form clusters according to their intracellular localizations [4]. Here, we performed the hierarchical cluster analysis of eukaryotic Rab GTPases stored in the KEGG/GENES database by considering their intracellular localizations and also the clusters of SNAREs in order to examine a possible increase of the numbers of Rab paralogs through the evolution.