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. Author manuscript; available in PMC: 2010 Nov 1.
Published in final edited form as: Neurobiol Dis. 2009 Aug 20;36(2):374–383. doi: 10.1016/j.nbd.2009.08.003

Figure 6. Schematic representations of Rab11 cycles in WT and HD conditions.

Figure 6

Left panel depicts the two cycles of Rab11 that are required for its proper function (normal). Rab11 associates and dissociates with membranes and alternates between GDP-bound inactive and GTP-bound active states. In the cytoplasm, GDP-bound Rab11 partners with Rab-GDP dissociation inhibitor (GDI). To fulfill functions, Rab11-GDP is recruited onto endosomal membranes for activation by a guanine nucleotide exchange factor (GEF) and conversion into GTP-bound form. After fulfilling the function by recruiting a cohort of effectors, Rab11-GTP is inactivated by a GTPase-activating protein (GAP) and returns back to GDP-bound form that is extracted by RabGDI. Right panel shows a proposed model for Rab11 dysfunction in HD. The key event causing neurodegeneration is a deficient nucleotide conversion from Rab11GDP to Rab11GTP or deficient activation of Rab11 (indicated by long dashed arrow), which occurs on endosomal membranes. Another problem in HD endosomal membranes is the accumulation of inactive GDP-bound form of Rab11 (enlarged oval) caused in part by reduced extraction of RabGDP by RabGDI (indicated by short dashed arrow). The role of the accumulation of Rab11GDP to neuronal dysfunction is unclear.