An Rtn4/Nogo-A-interacting micropeptide modulates synaptic plasticity with age

Abstract

100-250 amino acid 'micropeptides' are hidden throughout mammalian genomes, though few functional studies of micropeptides are published. Here, we describe a micropeptide known as the Plasticity Associated Neural Transcript Short (Pants), located in the 22q11.2 region of the human genome, the microdeletion of which conveys a high risk for schizophrenia. Our data show that Pants is upregulated in early adulthood in the mossy fiber circuit of the hippocampus, where it exerts a powerful negative effect on long-term potentiation (LTP). Pants is secreted from neurons, where it associates with synapses but is rapidly degraded with stimulation. Pants dynamically interacts with Rtn4/Nogo, a well-studied regulator of adult plasticity. This study shows that neural micropeptides can act as architectural modules that increase the diversity of the known proteome.