Protocadherin-?C2 is required for diffuse projections of serotonergic axons.

ABSTRACT: Serotonergic axons extend diffuse projections throughout various brain areas, and serotonergic system disruption causes neuropsychiatric diseases. Loss of the cytoplasmic region of protocadherin-? (Pcdh-?) 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-? member(s) are responsible for the phenotype is unknown. Here we demonstrated that Pcdh-?C2 (?C2), a Pcdh-? isoform, was highly expressed in serotonergic neurons, and was required for normal diffusion in single-axon-level analyses of serotonergic axons. The loss of ?C2 from serotonergic neurons, but not from their target brain regions, led to unbalanced distributions of serotonergic axons. Our results suggest that ?C2 expressed in serotonergic neurons is required for serotonergic axon diffusion in various brain areas. The ?C2 extracellular domain displays homophilic binding activity, suggesting that its homophilic interaction between serotonergic axons regulates axonal density via ?C2's cytoplasmic domain.

SUBMITTER: Katori S 

PROVIDER: S-EPMC5698425 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature