Rab Proteins and the Organization of Organelle Membrane Domains - Ras Superfamily Small G Proteins: Biology and Mechanisms 2 - page 19

Secondary Rab GTPase efectors

Cargo

Lipids SNAREs

Arf/Arl
GTPases

Coats

Rab GAPs

Rab B Rab A

Rab GEFs

Tethers

Motors

PI-metabolizing
enzymes

Primary Rab GTPase efectors

Fig. 2.2 Rab GTPases play a central role in the formation of membrane domains. Here we
describe a Rabcentric model summarizing the known possible interactions ( lines ) of Rabs
GTPases with other membrane-defining factors. Rab proteins ( purple ) directly interact with
GAPs and GEFs ( orange ), which often show activity towards up or downstream Rab GTPases.
Thereby Rab cascades are created, ensuring vectorial flow of membranes and proteins within the
cell. In addition, Rabs GTPases directly interact with tethers, PI-metabolizing enzymes, motors,
and membrane-deforming proteins ( blue ). Through these primary effectors, Rab GTPases indi-
rectly bind to, amongst others, other small GTPases, lipids, cargo, SNAREs, and coats ( green ).
Through cooperative interactions between Rab GTPases and primary and secondary effectors,
defined membrane domains are formed with critical roles in membrane trafficking and signaling

the last eukaryotic common ancestor (LECA) expressed between 20 and 23 Rab
paralogues (Elias et al. 2012 ; Kl ¨ pper et al. 2012 ) (Fig. 2.1 , underlined). The LECA
was probably highly advanced as it contained Rab proteins important for pathways
like endocytosis, exocytosis, and ciliary sorting (Fig. 2.1 , highlighted and labeled
by the functional group) (Elias et al. 2012 ; Kl¨pper et al. 2012 ). In addition to Rab
proteins, many other components of the transport machinery, such as coat and
tethering proteins, are also highly conserved (Field et al. 2011 ; Yu and Hughson
2010 ). Therefore, the basic mechanisms of membrane transport were established
early during eukaryotic evolution and Rab GTPases likely played a defining role in
this process.