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Internalization of D 2 dopamine receptors is clathrin‐dependent and select to dendro–axonic appositions in primate prefrontal cortex
Author(s) -
Paspalas Constantinos D.,
Rakic Pasko,
GoldmanRakic Patricia S.
Publication year - 2006
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2006.05023.x
Subject(s) - internalization , clathrin , neuroscience , endocytosis , dopamine , receptor , microbiology and biotechnology , biology , neurotransmitter , neurotransmitter receptor , endosome , central nervous system , biochemistry
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 D 2 receptors (D 2 Rs) 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 D 2 Rs or any other neurotransmitter receptor in the primate brain. We have captured in situ the insertion of D 2 Rs 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 D 2 Rs. The selective association of D 2 Rs 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 D 2 R signalling in mental illness.