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Accueil > Bibliographie > Axonal Targeting of the 5-HT(1B) Serotonin Receptor Relies on (...)

Axonal Targeting of the 5-HT(1B) Serotonin Receptor (...)

Traffic. 2011 Nov ;12(11):1501-20
Axonal Targeting of the 5-HT(1B) Serotonin Receptor Relies on Structure-Specific Constitutive Activation.
Carrel D, Simon A, Emerit MB, Rivals I, Leterrier C, Biard M, Hamon M, Darmon M, Lenkei Z.

By analogy to other axonal proteins, transcytotic delivery following spontaneous endocytosis from the somatodendritic membrane is expected to be essential for polarized distribution of axonal G-protein coupled receptors (GPCRs). However, possible contribution from constitutive activation, which may also result in constitutive GPCR endocytosis, is poorly known. Using two closely related but differentially distributed serotonin receptors, here we demonstrate higher constitutive activation and spontaneous endocytosis for the axonal 5-HT(1B) R, as compared to the somatodendritic 5-HT(1A) R, both in non-neuronal cells and neurons. Activation-dependent constitutive endocytosis is crucial for axonal targeting, because inverse-agonist treatment, which prevents constitutive activation, leads to atypical accumulation of newly synthesized 5-HT(1B) Rs on the somatodendritic plasma membrane. Using receptor chimeras composed of different domains from 5-HT(1A) R and 5-HT(1B) R, we show that the complete third intracellular loop of 5-HT(1B) R is necessary and sufficient for constitutive activation and efficient axonal targeting, both sensitive to inverse-agonist treatment. These results suggest that activation and targeting of 5-HT(1B) Rs are intimately interconnected in neurons.


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