In the rodent brain, certain G protein-coupled receptors and adenylyl cyclase type 3 are known to localize to the neuronal primary cilium, a primitive sensory organelle protruding singly from almost all neurons. A recent chemical screening study demonstrated that many compounds targeting dopamine receptors regulate the assembly of Chlamydomonas reinhardtii flagella, structures which are analogous to vertebrate cilia. Here we investigated the effects of dopaminergic inputs loss on the architecture of neuronal primary cilia in the rodent striatum, a brain region that receives major dopaminergic projections from the midbrain. We first analyzed the lengths of neuronal cilia in the dorsolateral striatum of hemi-parkinsonian rats with unilateral lesions of the nigrostriatal dopamine pathway. In these rats, the striatal neuronal cilia were significantly longer on the lesioned side than on the non-lesioned side. In mice, the repeated injection of reserpine, a dopamine-depleting agent, elongated neuronal cilia in the striatum. The combined administration of agonists for dopamine receptor type 2 (D2) with reserpine attenuated the elongation of striatal neuronal cilia. Repeated treatment with an antagonist of D2, but not of dopamine receptor type 1 (D1), elongated the striatal neuronal cilia. In addition, D2-null mice displayed longer neuronal cilia in the striatum compared to wild-type controls. Reserpine treatment elongated the striatal neuronal cilia in D1-null mice but not in D2-null mice. Repeated treatment with a D2 agonist suppressed the elongation of striatal neuronal cilia on the lesioned side of hemi-parkinsonian rats. These results suggest that the elongation of striatal neuronal cilia following the lack of dopaminergic inputs is attributable to the absence of dopaminergic transmission via D2 receptors. Our results provide the first evidence that the length of neuronal cilia can be modified by the lack of a neurotransmitter's input.

This study reveals that PRMT1 regulates the interaction between SCYL1 and γ₂-COP for Golgi organization via SCYL1 arginine methylation. We propose that SCYL1 arginine methylation by PRMT1 contributes to axon and dendrite morphogenesis in neurons. This report contributes to the elucidation of brain development via arginine methylation.

The primary cilium, an immotile protrusion of vertebrate cells, detects chemical and mechanical stimuli in the extracellular milieu and transduces them into the cell body, thereby contributing to cellular development and homeostasis. In the mammalian brain, serotonin receptor type 6 (Htr6) and other specific G protein-coupled receptors (GPCRs) localize preferentially to primary cilia and function in ciliary chemical detection; however, the molecular mechanism by which a subset of GPCRs is transported to primary cilia has not been fully elucidated. In the present study, we demonstrate that a region in the fourth intracellular domain of Htr6 (Htr6 i4) is sufficient for ciliary localization. In yeast, the interaction of this region with the C-terminal region of γ1-Adaptin, a subunit of adaptor protein complex 1 (AP-1), was identified. The interaction between Htr6 and γ1-Adaptin was confirmed by immunoprecipitation analysis using HEK293T cells. The preference for ciliary localization of Htr6 and Htr6 i4 was significantly decreased by ablation of γ1-Adaptin in hTERT RPE-1 cells, which was rescued by exogenous expression of γ1-Adaptin. Furthermore, Htr6 and Htr6 i4 showed reduced localization to primary cilia in γ1-Adaptin-depleted cultured hippocampal neurons compared with control neurons. These results indicate that the ciliary localization of Htr6 is facilitated by AP-1-mediated membrane trafficking.