Functional role(s) of phagosomal Rab GTPases

Abstract

Rab GTPases are at the central node of the machinery that regulates trafficking of organelles, including phagosomes. Thanks to the unique combination of high quality phagosome purification with highly sensitive proteomic studies, the network of Rab proteins that are dynamically associated with phagosomes during the process of maturation of this organelle is relatively well known. Whereas the phagosomal functions of many of the Rab proteins associated with phagosomes are characterized, the role(s) of most of these trafficking regulators remains to be identified. In some cases, even when the function in the context of phagosome biology is described, phagosomal Rab proteins seem to have similar roles. This review summarizes the current knowledge about the identity and function of phagosomal Rab GTPases, with a particular emphasis on new evidence that clarify these seemingly overlapping Rab functions during phagosome maturation.

Keywords: Rab; autophagosome; bacteria; lysosome; phagosome.

Figure 1. The network of phagosomal Rab GTPases: the most common Rab proteins. This model shows the functional link between Rab proteins associated with phagosomes, interactions with different intracellular compartments and/or cytoskeletal components. As discussed in the text, studies have shown that seemingly overlapping functions are in fact more specific. MTs, microtubules; ER, endoplasmic reticulum.

Figure 2. The network of phagosomal Rab GTPases: the less common Rab proteins. This model shows the potential functional link between Rab proteins associated with phagosomes and the putative interactions with different intracellular compartments and/or cytoskeletal components.

Figure 3. The core vs. accessory network of phagosomal Rab GTPases. Proposed model for the observed functional association of multiple Rab GTPases to phagosomes. A group of ‘core’ Rab GTPases regulates the default maturation of the phagosomes as housekeeping Rab proteins (indicated in red and green). Another group, called here accessory Rab GTPases could have a functional impact in a more regulated manner (indicated in brown, purple and orange). First, activation via some intracellular (not depicted) and extracellular signals (shown as ‘signal A’) can change the fate of the phagosome and consequently the function triggered by the origin signal. Alternatively, different intracellular signals e.g., present and/or activated in different cell types (shown as ‘signal B’) can modulate the default maturation. Finally, compelling evidence indicates that pathogen-driven recruitment (either after activation of receptors or secreting bacterial factors, shown as ‘signal C’) of Rab GTPases can change the phagosomal fate facilitating bacterial survival. The model is simplified and does not include well-known situations in which the pathogen-subverted Rab functions are in fact from the core machinery.