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

First Author  Kragness S Year  2022
Journal  PLoS One Volume  17
Issue  6 Pages  e0269404
PubMed ID  35771867 Mgi Jnum  J:331499
Mgi Id  MGI:7311075 Doi  10.1371/journal.pone.0269404
Citation  Kragness S, et al. (2022) An Rtn4/Nogo-A-interacting micropeptide modulates synaptic plasticity with age. PLoS One 17(6):e0269404
abstractText  Micropeptides, encoded from small open reading frames of 300 nucleotides or less, are hidden throughout mammalian genomes, though few functional studies of micropeptides in the brain 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). Further, we find that Pants is secreted from neurons, where it associates with synapses but is rapidly degraded with stimulation. Pants dynamically interacts with Rtn4/Nogo-A, a well-studied regulator of adult plasticity. Pants interaction with Nogo-A augments its influence over postsynaptic AMPA receptor clustering, thus gating plasticity at adult synapses. This work shows that neural micropeptides can act as architectural modules that increase the functional diversity of the known proteome.
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