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17.8: Rab Cascades

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Cell Biology

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Rab Cascades

17.8: Rab Cascades

Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.

Rabs recruit a unique set of peripheral proteins called Rab effectors that mediate vesicle movement and regulate membrane traffic in their associated compartments, thus establishing a distinctive subcellular localization pattern. One Rab recruits the corresponding GEF that sequentially activates the next Rab along a Rab cascade pathway in its GTP-bound active state. In the cascade, Rab GAPs work in a fashion countering the Rab GEFs to complete the Rab conversions. Scientists describe this hypothesis that in a pathway, the activation of one Rab will recruit the GAP that inactivates the preceding Rab, thus reducing the overlap between adjacent Rab domains in a pathway.

Rab cascades establish the order of compartments during cargo progression between the organelles in the secretory pathway. Rab domains contact their effectors in a sequence, generating directional Rab cascades. The discovery of Rab cascades in the Golgi and the possible homotypic fusion of all membrane-bound Golgi compartments have led to a new model for protein transport in the Golgi.

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Keywords: Rab GTPases Membrane Fusion GTP GDP Molecular Switches Tethering Proteins SNARE Complex Rab Effectors Rab GEF Rab GAP Rab Cascades Secretory Pathway Golgi

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