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Internalization of D 2 dopamine receptors is clathrin‐dependent and select to dendro–axonic appositions in primate prefrontal cortex

Internalization of D 2 dopamine receptors is clathrin‐dependent and select to dendro–axonic... Much of our knowledge on trafficking of neurotransmitter receptors derives from heterologous expression systems and neurons in vitro. Understanding these dynamics in vivo for dopamine receptors, and D2 receptors (D2Rs) in particular, presents a foremost challenge as their pharmacological manipulation underlies antipsychotic medications and drug abuse, which may in turn alter response to endogenous dopamine. Here we present the first ultrastructural evidence of clathrin‐mediated endocytosis of D2Rs or any other neurotransmitter receptor in the primate brain. We have captured in situ the insertion of D2Rs in clathrin‐coated membrane pits, resulting in receptor sorting in primary endosomes. Endocytosis was specific to nonsynaptic membranes of distal dendrites, and virtually absent from larger shafts, spines, axons and perikarya expressing D2Rs. The selective association of D2Rs with the clathrin endocytotic pathway of high‐order dendrites identifies a novel substrate for monitoring and adjusting dopaminoception, as well as a potent target for dysregulation, and manipulation, of D2R signalling in mental illness. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Neuroscience Wiley

Internalization of D 2 dopamine receptors is clathrin‐dependent and select to dendro–axonic appositions in primate prefrontal cortex

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References (46)

Publisher
Wiley
Copyright
Copyright © 2006 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0953-816X
eISSN
1460-9568
DOI
10.1111/j.1460-9568.2006.05023.x
pmid
16987224
Publisher site
See Article on Publisher Site

Abstract

Much of our knowledge on trafficking of neurotransmitter receptors derives from heterologous expression systems and neurons in vitro. Understanding these dynamics in vivo for dopamine receptors, and D2 receptors (D2Rs) in particular, presents a foremost challenge as their pharmacological manipulation underlies antipsychotic medications and drug abuse, which may in turn alter response to endogenous dopamine. Here we present the first ultrastructural evidence of clathrin‐mediated endocytosis of D2Rs or any other neurotransmitter receptor in the primate brain. We have captured in situ the insertion of D2Rs in clathrin‐coated membrane pits, resulting in receptor sorting in primary endosomes. Endocytosis was specific to nonsynaptic membranes of distal dendrites, and virtually absent from larger shafts, spines, axons and perikarya expressing D2Rs. The selective association of D2Rs with the clathrin endocytotic pathway of high‐order dendrites identifies a novel substrate for monitoring and adjusting dopaminoception, as well as a potent target for dysregulation, and manipulation, of D2R signalling in mental illness.

Journal

European Journal of Neuroscience – Wiley

Published: Sep 1, 2006

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