About this Research Topic
The secretory and endocytic pathways of Eukaryotic cells are composed of multiple distinct membrane-bound compartments. Trafficking between these compartments is dynamic and tightly regulated. Perhaps the most prominent form of trafficking regulation involves GTPases, which act as molecular switches to turn trafficking pathways on or off. There are two main families of “small” GTPases that regulate trafficking events, the Arf family and the Rab family. The human genome encodes approximately 20 Arf family members and 70 Rab family members. Both Arf and Rab GTPases are regulated by GEFs (guanine nucleotide exchange factors) that activate the GTPases by catalyzing their release of GDP to bind GTP. Once activated through GTP-binding, Arf and Rab GTPases are stably bound to the membrane surface and function by recruiting downstream effector proteins that serve to generate, transport, and tether vesicular and tubular membrane carriors. Arf and Rab GTPases are subsequently inactivated via stimulation of GTP hydrolysis by GAPs (GTPase-activating proteins), and the resulting GDP-bound GTPases dissociate from the membrane surface.
The sites of action for many Arfs and Rabs have been identified, and the pathways and effectors controlled by many of these GTPases are known. Similarly, many GEFs and GAPs that regulate Arf and Rab GTPases are known, and the basic molecular mechanisms underlying the actions of nucleotide exchange and GTP hydrolysis have been characterized. However, there are many “orphaned” Rabs for which the corresponding GEF and/or GAP has not been clearly identified. Furthermore, there are many interesting unanswered questions regarding how GEFs and GAPs are themselves regulated: How are GEFs and GAPs recruited to their site of action? How is their activity controlled? What is the molecular logic that underlies the regulation of GEFs and GAPs? How common is cross-talk between different GTPase pathways? This Research Topic will focus on these emerging areas of research into the biology of trafficking GTPases.
Keywords: eukaryotic cells, trafficking, GTPases, endocytic pathways, membrane-bound compartments