Figure 9. Schematic summarising main findings.

Polarised surface distribution of CB1R is established and maintained by two complementary mechanisms: (Ai) selective delivery of newly synthesized CB1R to the axon (or restricted delivery to dendrites) and (Aii) selective retention in axons and retrieval from dendrites. The C-terminal motif Helix 9 plays a role in both of these mechanisms because deletion of H9 leads to: (Bi) a loss of axon-selective delivery and (Bii) reduced retention in both axons and dendrites that can be reversed in dendrites by inverse agonist application, suggesting that CB1R^ΔH9 is more susceptible to activity-driven internalisation.