Psychiatry related information on DRD1IP

• Association of the calcyon gene (DRD1IP) with attention deficit/hyperactivity disorder [1].

High impact information on DRD1IP

• Dual signaling regulated by calcyon, a D1 dopamine receptor interacting protein [2].
• Calcyon localizes to dendritic spines of D1 receptor-expressing pyramidal cells in prefrontal cortex [2].
• These studies delineate a mechanism of Gq- and Gs-coupled heterotrimeric GTP-binding protein-coupled receptor cross talk by which D1 receptors can shift effector coupling to stimulate robust intracellular calcium (Ca2+i) release as a result of interaction with calcyon [2].
• The discovery that two DRIPs, calcyon and neuronal Ca(2+) sensor 1 (NCS-1), are upregulated in schizophrenia highlights the possibility that altered protein interactions and defects in Ca(2+) homeostasis might contribute to abnormalities in the brain dopamine system in neuropsychiatric diseases [3].
• RESULTS: The dorsolateral prefrontal cortex in schizophrenic patients displayed nearly twice the normal levels of calcyon, whereas filamin-A and spinophilin levels were unaltered [4].

Biological context of DRD1IP

• In addition, surface biotinylation and luminescence assays revealed that priming stimulates a 2-fold increase in the levels of calcyon expressed on the cell surface and that subsequent D1R activation produces further accumulation of the protein in the plasma membrane [5].
• As these two variants are not predicted to alter calcyon function, we screened the gene exons by sequencing [1].
• These findings support the proposed involvement of the calcyon gene in ADHD and implicate haplotype C1 as containing a risk allele [1].
• Two single nucleotide polymorphisms (SNPs) at the CALCYON locus were genotyped in 70 AA and 206 EA individuals with schizophrenia and 90 AA and 118 EA individuals with cocaine dependence [6].
• Up-regulation of the D1 dopamine receptor-interacting protein, calcyon, in patients with schizophrenia [4].

Anatomical context of DRD1IP

• The role of calcyon in potentiating Ca2+-dependent signaling should provide insight into the D1 receptor-modulated cognitive functions of prefrontal cortex [2].
• The present work shows that calcyon is constitutively localized both in vesicular and plasma membrane compartments within HEK293 cells [5].
• The effects of priming and D1R agonists were blocked by nocodazole implicating microtubules in the delivery of calcyon-containing vesicles to the cell surface [5].
• There was a high degree of overlap in the distribution of LC and calcyon in neuronal dendrites, spines, and cell bodies [7].
• Dopaminergic abnormalities in select thalamic nuclei in schizophrenia: involvement of the intracellular signal integrating proteins calcyon and spinophilin [8].

Associations of DRD1IP with chemical compounds

• Accumulation of calcyon in the plasma membrane correlated well with increased intracellular calcium levels as thapsigargin mimicked, and 2-aminoethoxydiphenylborane abrogated, the effects of priming [5].
• CALCYON gene variation, schizophrenia, and cocaine dependence [6].

Physical interactions of DRD1IP

• Specifically, we examined whether the D1 dopamine receptor-interacting protein calcyon and the D2 dopamine receptor-interacting proteins filamin-A and spinophilin are affected in the dorsolateral prefrontal cortex of patients with schizophrenia [4].

Other interactions of DRD1IP

• Calcyon is called a "cross-talk accessory protein" because the mechanism by which it enables the typically Gs-linked D1 dopamine receptor to stimulate intracellular calcium release depends on a priming step involving heterologous Gq-linked G-protein-coupled receptor activation [5].
• Only three of the candidates-DRD5, 5HTT, and CALCYON-coincided with sites of positive linkage identified by our screen [9].
• Furthermore, schizophrenia-associated alterations in the levels of calcyon and NCS-1 messages were correlated [10].

Analytical, diagnostic and therapeutic context of DRD1IP

• Co-immunoprecipitation studies further suggested an association of calcyon with the clathrin-mediated endocytic machinery [7].

References