The Rab11-Rabin8-Rab8 ciliogenesis complex regulates the expansion of cilia-derived light-sensing organelles, the rod outer segments, via post-Golgi rhodopsin transport carriers (RTCs). Rabin8, an effector of Rab11 and a nucleotide exchange factor (GEF) for Rab8, is phosphorylated at S272 by NDR2 kinase (aka STK38L), a canine erd gene product linked to the human ciliopathy Leber congenital amaurosis (LCA). Here, we define the step at which NDR2 phosphorylated Rabin8 regulates Rab11-Rab8 succession in X. laevis transgenic rod photoreceptors expressing human GFP-Rabin8 and its mutants. GFP-Rabin8 accumulates with endogenous Rabin8 at the Golgi-apposed exit sites (GESs), aka the trans-Golgi network (TGN). Rabin8 mutants deficient in Rab11 binding prevent membrane association of GFP-Rabin8. GFP-Rabin8 and NDR2 kinase interact with RTC-R-SNARE-VAMP7 at the trans-Golgi and the GESs. Here, GFP-Rabin8 and GFP-Rabin8-S272E phosphomimetic are integrated into RTCs, which are subsequently functionalized by Rabin8 Rab8 GEF activity. Non-phosphorylatable GFP-Rabin8-S272A causes significant GES enlargement and deformation, possibly leading to unconventional membrane advancement toward the cilium, bypassing RTCs. Rabin8 phosphorylation loss due to an NDR2/STK38L gene disruption likely causes dysfunctional rhodopsin Golgi-to-cilia trafficking underlying retinal degeneration and early-onset blindness.

Keywords:
Cilium, Rab GTPases, Sensory Receptors, Rhodopsin
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© 2025. Published by The Company of Biologists
2025
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