Protocadherin-αC2 is required for diffuse projections of serotonergic axons. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Katori, Shota; Noguchi-Katori, Yukiko; Okayama, Atsushi; Kawamura, Yoshimi; Luo, Wenshu; Sakimura, Kenji; Hirabayashi, Takahiro; Iwasato, Takuji; Yagi, Takeshi
• Is Part Of: Scientific reports. Volume 7:Issue 1(2017)
• Page Start: 1
• Page End: 14
• Publication Date: 2017-12
• Subjects: Natural history -- Research -- Periodicals; Biology -- Research -- Periodicals; Physical sciences -- Research -- Periodicals; Earth sciences -- Research -- Periodicals; Environmental sciences -- Research -- Periodicals; 502.85
• DOI: 10.1038/s41598-017-16120-y
• Languages: English
• ISSNs: 2045-2322

Abstract

Abstract Serotonergic axons extend diffuse projections throughout various brain areas, and serotonergic system disruption causes neuropsychiatric diseases. Loss of the cytoplasmic region of protocadherin-α (Pcdh-α) family proteins, products of the diverse clusteredPcdh genes, causes unbalanced distributions (densification and sparsification) of serotonergic axons in various target regions. However, whichPcdh-α member(s) are responsible for the phenotype is unknown. Here we demonstrated thatPcdh-αC2 (αC2 ), aPcdh-α isoform, was highly expressed in serotonergic neurons, and was required for normal diffusion in single-axon-level analyses of serotonergic axons. The loss of αC2 from serotonergic neurons, but not from their target brain regions, led to unbalanced distributions of serotonergic axons. Our results suggest that αC2 expressed in serotonergic neurons is required for serotonergic axon diffusion in various brain areas. The αC2 extracellular domain displays homophilic binding activity, suggesting that its homophilic interaction between serotonergic axons regulates axonal density via αC2′s cytoplasmic domain.