Identification of Two Functionally Distinct Endosomal Recycling Pathways for Dopamine D2Receptor

• DOI: 10.1523/jneurosci.0008-12.2012
• Publication Date: 2012-05-23T17:10:27Z
• Authors: Yun Li; Brittany D. Roy; Wei Wang; Li Zhang; Lifeng Zhang; Stephen B. Sampson; Yupeng Yang; Da-Ting Lin
• Keywords: Medium spiny neuron; Internalization

Dopamine D₂ receptor (DRD2) is important for normal function of the brain reward circuit. Lower DRD2 in increases risk substance abuse, obesity, attention deficit/hyperactivity disorder, and depression. Moreover, target most antipsychotics currently use. It well known that dopamine-induced endocytosis its desensitization. However, it remains controversial whether recycled back to plasma membrane or targeted degradation following dopamine stimulation. Here, we used total internal reflection fluorescent microscopy (TIRFM) image with a superecliptic pHluorin tagged N terminus. With these technical advances, were able directly visualize vesicular insertion events cultured mouse striatal medium spiny neurons. We showed occurs on neuronal somatic dendritic surfaces. Lateral diffusion was observed insertion. Most importantly, using our new approach, uncovered two functionally distinct recycling pathways DRD2: constitutive pathway activity-dependent pathway. further demonstrated Rab4 plays an role recycling, while Rab11 required recycling. Finally, play roles determining function: Rab4-sensitive determines steady-state surface expression levels DRD2, whereas Rab11-sensitive functional resensitization DRD2. Our findings underscore significance endosomal regulation function.