Format

Send to

Choose Destination
Sci Rep. 2017 Nov 21;7(1):15908. doi: 10.1038/s41598-017-16120-y.

Protocadherin-αC2 is required for diffuse projections of serotonergic axons.

Author information

1
KOKORO-Biology, Laboratories for Integrated Biology, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka, 565-0871, Japan.
2
Division of Neurogenetics, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka, 411-8540, Japan.
3
Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Sinjuku, Tokyo, 113-0021, Japan.
4
Department of Genetics, SOKENDAI (The Graduate University for Advanced Studies), Mishima, Shizuoka, 411-8540, Japan.
5
Department of Cellular Neurobiology, Brain Research Institute, Niigata University, 1-757 Asahimachidoori, Chuoku, Niigata, 951-8585, Japan.
6
KOKORO-Biology, Laboratories for Integrated Biology, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka, 565-0871, Japan. yagi@fbs.osaka-u.ac.jp.
7
AMED-CREST, Tokyo, 100-0004, Japan. yagi@fbs.osaka-u.ac.jp.

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 clustered Pcdh genes, causes unbalanced distributions (densification and sparsification) of serotonergic axons in various target regions. However, which Pcdh-α member(s) are responsible for the phenotype is unknown. Here we demonstrated that Pcdh-αC2 (αC2), a Pcdh-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.

PMID:
29162883
PMCID:
PMC5698425
DOI:
10.1038/s41598-017-16120-y
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center