Practice question

Before trans-SNARE zippering drives bilayer merger vesicles must be captured near correct target ensuring compartment identity maintained despite promiscuous SNAREs. Rab GTPases provide master specificity for docking stage. Active GTP-bound form on vesicle or target exposes switch regions binding effectors. Examples: Rab1-GTP recruits p115 and GM130 at ER-to-Golgi interface forming extended coiled-coil tether over 200 nm, Rab5-GTP recruits EEA1 and Rabenosyn-5 containing FYVE domains binding PI3P plus alpha helical tether, Rab6 recruits GCC185, Rab7 recruits HOPS complex VPS11-18-39-41. This physical bridging reduces dimensionality searching, proofreads identity, increases local concentration promoting cognate SNARE engagement. Clathrin forms coats for sorting at plasma membrane and TGN, alpha-mannosidase trims N-glycans in Golgi, and SNARE disassembly factors NSF and alpha-SNAP act post-fusion regenerating SNAREs. Rab conversion mediated by GEFs Mon1-Ccz1 and GAPs ensures directionality; Rab5 to Rab7 conversion guides endosome maturation early to late. Ablation of Rab or tether leads to mistargeting and vesicle accumulation despite intact SNAREs present and functional.