Rab Proteins and the Organization of Organelle Membrane Domains - Ras Superfamily Small G Proteins: Biology and Mechanisms 2 - page 18

Ciliar or lagellar Ciliar or lagellar

traic traic

Early endosomal Early endosomal

traic

Rab3
Rab12
Rab26

traic

Cilium or
Flagellum
Rab8
Rab28
RabL4/IFT27

Rab5
Rab21
Rab22
Rab24

Early Endosome

Secretory Vesicles

Rab35

Secretion Endocytic recycling

Rab2
Rab4
Rab11
Rab14

Endosome
to Golgi traic

Endosome

to Golgi traic

Recycling Endosomes

Rab6

Golgi

Late endosomal Late endosomal

traic

Rab1
Rab2
Rab8

Rab10
Rab18

traic

Late Endosome

Rab7
Rab9

Endoplasmic
Reticulum
Rab1
Rab2

Lysosome
and Related
Organelles

Rab24
Rab30

Rab7 Rab32
Rab23 Rab38
Rab27

Nucleus

Fig. 2.1 Compartmentalization of Rab GTPases within eukaryotic cells. Rab GTPases are
localized to specific organelles. Six Rab supergroups that were defined by Kl¨pper (Kl¨pper
et al. 2012 ) are highlighted as functional groups. Underlined Rab GTPases were identified to be
present in the LECA in both the studies of Elias et al. ( 2012 ) and Kl¨pper et al. ( 2012 ).
Figure adapted from Stenmark (Stenmark 2012 ). Rab GTPase localizations are derived from
(Galvez et al. 2012 ; Stenmark 2009 ; Hutagalung and Novick 2011 )

during cargo transport. We will end by discussing the contribution of Rab proteins
to the regulation of signaling.

2.2 Evolution of the Rab GTPase Family

The importance of Rab GTPases is illustrated by the fact that they are evolutionarily
conserved. This strongly suggests they played a critical role in endomembrane
evolution (Gurkan et al. 2007 ). Interestingly, the number of Rab GTPases dramat-
ically changed between species with both gains and losses. In mammalian cells,
more than 60 Rab GTPases have been identified whereas in fungi, there are between
8 and 12 depending on the species (Pereira-Leal 2008 ; Kl¨pper et al. 2012 ; Stein
et al. 2012 ). The loss can in some instances be correlated with changes in cellular
organization, such as the concomitant loss of cilia and ciliary Rabs proteins, but this
is not always the case (Kl¨pper et al. 2012 ). Recently, several groups proposed that