Rab effector

Secl/Muncl8-like proteins), Rab-proteins, and Rab-effectors (Jahn et al., 2003). The specific isoforms of these proteins that are being used vary tremendously between fusion reactions, but the general principle by which these proteins act seems to be always similar Rab and Rab-effector proteins appear to proofread the docking and fusion reaction between the two target membranes and may even mediate the docking at least in part, whereas SNARE- and SM-proteins catalyze the actual fusion reaction. 

De Renzis S, Sonnichsen B, Zerial M. 2002. Divalent Rab effectors regulate the sub-compartmental organization and sorting of endosomes. Nature Cell Biol 4 124-133 De Robertis EM, Sasai Y. 1996. A common plan for dorsoven-tral patterning in Bilateria. Nature 380 37-40 DeRosse P, Funke B, Burdick KE, Lencz T, Ekholm JM, et al. 

Diao, A., Rahman, D., Pappin, D.J., Lucocq, J. and Lowe, M. (2003) The coiled-coil membrane protein golgin-84 is a novel rab effector required for Golgi ribbon formation. J. Cell Biol. 160, 201-212. 

A second set of GTP-binding proteins, the Rab proteins, regulate docking of vesicles with the correct target membrane. Each Rab appears to bind to a specific Rab effector, a typically long colled-coil protein, associated with the target membrane. 

Christoforidis, S., and Zerial, M. (2000). Purification and identification of novel Rab effectors using affinity chromatography. Methods 20, 403-410. 

Membrane-bound GTP rabs recruit effectors to the membrane. In neurons and neuroendocrine cells, the vesicle-associated Rab3 binds to rabphilin and to RIM. RIM is a component of the presynaptic cytomatrix and may thus serve as a docking receptor for synaptic vesicles at the active zone. 

Spang, A. Vesicle transport a close collaboration of Rabs and effectors. Curr. Biol. 14 R33-R34, 2004. 

Fig. 4 Stages in synaptic vesicle exocytosis. Putative intermediate steps on the molecular pathway to synaptic vesicle fusion. Vesicle delivery and tethering to the presynaptic membrane most likely involves Rab-proteins and their effectors. So far, the nature of a speculative docking complex (dc) is unclear, but docking appears to be independent from SNARE proteins. In the primed state, SNAREs have assembled into a complex probably stabilized by complexin (Cpx). The fusion reaction is arrested until the intracellular calcium concentration increases. The putative calcium sensor for fast neurotransmitter release, synaptotagmin 1 (Syt), binds to intracellular calcium and in turn triggers fusion by associating with the presynaptic membrane and interacting with the SNARE complex, thereby displacing complexin (Tang et al. 2006).

Gallwitz D, Jahn R. (2003) The riddle of the Secl/Munc-18 proteins - new twists added to their interactions with SNAREs. Trends Biochem Sci 28 113-16 Grosshans BL, Ortiz D, Novick P (2006) Rabs and their effectors achieving specificity in membrane traffic. Proc Natl Acad Sci U S A 103 11821-7 Hanson PI, Whiteheart SW (2005) AAA+ proteins have engine, will work. Nat Rev Mol Cell Biol 6 519-29... 

Rab proteins between the cytosol and membranes is fadlitated by GDI. Both REP and GDI bind the GDP-bound inactive form of Rab. On the membrane, Rab proteins are activated by RabGEFs and deactivated by RabGAPs. In the active state, Rabs interact with structurally and functionally diverse effectors, including cargo sorting complexes on donor membranes, motor proteins involved in vesicular transport and tethering complexes that regulate vesicle fusion with acceptor membranes. 

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