The Rab family is by far the largest among the small GTPases, with more than 60 members in humans [1
]. Originally identified as regulators of membrane traffic in yeast, the Rabs have been found to regulate membrane traffic in a large number of species ranging from amoeba and yeast to plants, nematodes, insects, and humans [2
]. Different family members are known to localize to distinct organelle membranes in a reversible manner, and several regulators of Rab membrane association are known, including proteins that mediate the prenylation of one or two carboxy-terminal cysteine residues of the Rabs [1
]. There is no single mechanism by which Rab GTPases direct membrane traffic, although the switching between GTP- and GDP-bound forms (promoted by specific guanine nucleotide exchange factors and GTPase-activating proteins, respectively) is central to their function [1
]. In their GTP-bound form, Rab GTPases recruit effector proteins of various types, including membrane tethering factors, phosphatases, kinases, and cytoskeletal motors. The recruitment of these effectors to specific membranes at specific time points is the principal way by which Rabs control membrane dynamics and identity [1
]. Because this specificity requires the existence of many different Rabs that recruit distinct effectors, the issue of identifying and classifying different Rab family members in various organisms has excited considerable interest, and several excellent papers on this issue have already been published [2
]. Klöpper et al
. now present in BMC Biology
the most comprehensive phylogenetic study of Rabs so far [6
]. This study shows that, at the earliest identifiable point in eukaryotic evolution, the so-called last eukaryotic common ancestor (LECA) [7
], there was already a remarkably large number of different Rabs. Interestingly, Klöpper et al
. were able to classify the LECA Rabs into six supergroups (Figure ) that can be traced through evolution. This analysis may prove very valuable, not only for those studying Rabs, but also for all those interested in eukaryotic evolution.
Figure 1 Evolutionary tree depicting the relationships of the different Rab families proposed to have been present in the last eukaryotic common ancestor (LECA). (Figure reproduced from Figure 1 of Klöpper et al. .).