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How do Rab proteins ensure specificity in vesicle transport?

Biology Asked by tail_recursion on July 22, 2021

From this paragraph, from Molecular Biology of the Cell 6th Edition, the author makes it quite clear that Rab proteins are important for the specificity of vesicle transport and that Rab proteins are used as molecular markers that identify compartments. They also make it clear that for many membrane fusion events active Rab proteins are required on both sides of the reaction. What is not clear to me is how Rab proteins ensure specificity?

The author is not clear on how Rab proteins ensure specificity. The only way I can imagine this happening is that Rab proteins on the target membrane recognise Rab proteins or other molecular markers on the vesicle and only bind to appropriate markers, but the author does not clearly state this in the text.

Specificity in targeting is ensured because all transport vesicles display surface markers that identify them according to their origin and type of cargo, and target membranes display complementary receptors that recognize the appropriate markers.

What ‘surface markers’ and ‘complementary receptors’ is the author talking about here? Due to the position of the sentence in the paragraph below I’m inclined to think they are talking about Rab proteins and SNAREs.

To ensure an orderly flow of vesicle traffic, transport vesicles must be highly accurate in recognizing the correct target membrane with which to fuse. Because of the diversity and crowding of membrane systems in the cytoplasm, a vesicle is likely to encounter many potential target membranes before it finds the correct one. Specificity in targeting is ensured because all transport vesicles display surface markers that identify them according to their origin and type of cargo, and target membranes display complementary receptors that recognize the appropriate markers. This crucial process occurs in two steps. First, Rab proteins and Rab effectors direct the vesicle to specific spots on the correct target membrane. Second, SNARE proteins and SNARE regulators mediate the fusion of the lipid bilayers. Rab proteins play a central part in the specificity of vesicle transport. Like the coat-recruitment GTPases discussed earlier, Rab proteins are also monomeric GTPases. With over 60 known members, the Rab subfamily is the largest of the monomeric GTPase subfamilies. Each Rab protein is associated with one or more membrane-enclosed organelles of the secretory or endocytic path- ways, and each of these organelles has at least one Rab protein on its cytosolic surface. Their highly selective distribution on these membrane systems makes Rab proteins ideal molecular markers for identifying each membrane type and guiding vesicle traffic between them. Rab proteins can function on transport vesicles, on target membranes, or both.
Like the coat-recruitment GTPases, Rab proteins cycle between a membrane and the cytosol and regulate the reversible assembly of protein complexes on the membrane. In their GDP-bound state, they are inactive and bound to another protein (Rab-GDP dissociation inhibitor, or GDI) that keeps them soluble in the cytosol; in their GTP-bound state, they are active and tightly associated with the membrane of an organelle or transport vesicle. Membrane-bound Rab-GEFs activate Rab proteins on both transport vesicle and target membranes; for some membrane fusion events, activated Rab molecules are required on both sides of the reaction.

I read this article and it states that;

For its functions, active Rab5 must be localized to both endocytic vesicles and early endosomes.

In this case I can understand how Rab proteins ensure specificity in that Rab5 on the target membrane will only interact with an endocytic vesicle if it has Rab5 on its surface. But is this always the case? Will Rabs on a membrane always require certain Rabs or other molecules on the surface of a vesicle in order to tether and dock the vesicle? If not I can’t see how they are providing specificity to transport.

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