The Rabs: a family at the root of metazoan evolution

Abstract

Eukaryotic cells are distinguished by their compartmentalization into membrane-enclosed organelles that exchange membranes and content in a highly ordered manner. Central in defining membrane identity are the Rabs, a large family of small GTPases that localize to distinct membranes and recruit specific regulators of membrane traffic. Two recent papers, including one by Klöpper et al. in BMC Biology, present phylogenomic evidence that the Rab repertoire was established very early in eukaryotic evolution, and correlates with interspecies variations in organelles.

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. [6].).

Figure 2

The LECA Rabs and their proposed functions. A schematic LECA cell is shown with the routes controlled by the six Rab supergroups defined by Klöpper et al. [6] color-coded. The Rabs belonging to the respective groups are indicated below. Even though most of the Rabs have been retained in human cells, two have been lost (RabX1 and Rab29). Note that even if there is a good match between the phylogenetic grouping and the cellular pathways controlled by the respective Rabs, there are some possible misfits: Rab24 (group II) has been found to regulate autophagy; Rab23 (group III) has been described to regulate ciliary functions; Rab2 (group IV) was identified as a regulator of traffic in the early biosynthetic pathway; Rab6 (group V) has, in addition to regulating endosome-to-Golgi transport, also been implicated in intra-Golgi trafficking (see references in [1]). ER, endoplasmic reticulum.