Rab protein evolution and the history of the eukaryotic endomembrane system

Abstract

Spectacular increases in the quantity of sequence data genome have facilitated major advances in eukaryotic comparative genomics. By exploiting homology with classical model organisms, this makes possible predictions of pathways and cellular functions currently impossible to address in intractable organisms. Echoing realization that core metabolic processes were established very early following evolution of life on earth, it is now emerging that many eukaryotic cellular features, including the endomembrane system, are ancient and organized around near-universal principles. Rab proteins are key mediators of vesicle transport and specificity, and via the presence of multiple paralogues, alterations in interaction specificity and modification of pathways, contribute greatly to the evolution of complexity of membrane transport. Understanding system-level contributions of Rab proteins to evolutionary history provides insight into the multiple processes sculpting cellular transport pathways and the exciting challenges that we face in delving further into the origins of membrane trafficking specificity.

New insights in the regulation of Rab GTPases by G protein-coupled receptors

“…24 Post-translational modifications, such as the addition of one or two prenyl groups to the C-terminus is necessary for the initial targeting of Rab GTPases to membranes. 25,26 The transfer of a geranylgeranyl moiety from geranylgeranyl pyrophosphate to cysteines in Rab proteins with an -CAAX (where A is an aliphatic residue and X is any amino acid), -XXCC, -XCXC and -CCXX C-terminal is catalyzed by a specific Rab geranylgeranyltransferase (RGGT). Some Rab GTPases containing a -CAAX motif were reported to be processed post-geranylgeranylation by proteolysis and methylation.…”

Expanding Proteostasis by Membrane Trafficking Networks

“…We now appreciate that these integrated coat, tether, and fusion (CTF) scaffolds, although evolutionarily conserved (Gurkan et al 2007;Dacks et al 2009;Brighouse et al 2010;Klute et al 2011;Elias et al 2012), are often unique and/or highly specialized for each cell type .…”

“…Our understanding of these endomembrane trafficking pathways has come from biological, biochemical, biophysical, and structural analysis of trafficking machineries that includes the coat systems that generate nascent compartments, the tethers that link diverse trafficking compartments together, and fusion components that direct content mixing (Box 2). These integrated coat, tether, fusion (CTF) scaffolds, although evolutionarily conserved (Gurkan et al 2007;Dacks et al 2009;Brighouse et al 2010;Klute et al 2011;Elias et al 2012), are often unique and specialized for each cell type . Moreover, the CTF system forms dynamic complexes that control the temporal and spatial features of endomembrane architecture and function through the information encoded by the primary polypeptide sequence, but presented in the context of the fold (the secondary, tertiary, and quaternary structural features) of each cargo (Nishimura et al 1999;Miller and Barlowe 2010;Kelly and Owen 2011).…”

Contrasting patterns in the evolution of the Rab GTPase family in Archaeplastida

“…Our understanding of the Rab function derives primarily from studies on a few selected models systems, primarily mammalian cells and the yeast Saccharomyces cerevisiae, but more limited knowledge exists also for other species representing different distantly related eukaryotic lineages, for example the kinetoplastid Trypanosoma brucei, the ciliate Tetrahymena thermophila, and the plant Arabidopsis thaliana [2][3][4]. One of the puzzling aspects of the biology of the Rab family is the fact that the total number of Rab genes may differ profoundly between different species: whereas some eukaryotic cells are able to secure their proper functioning with less than ten Rabs, other species exhibit tens or even hundreds of Rab paralogs [3,5].…”

“…Comparative genomic and phylogenetic studies revealed that a large number of distinct Rab paralogs have been established early in the evolution of eukaryotes [3,5,6]. Reconstructions of the Rab complement in the deepest point of the phylogeny of extant eukaryotes, i.e.…”