Collagen-derived matricryptins promote inhibitory nerve terminal formation in the developing neocortex

dc.contributor.authorSu, Jianminen
dc.contributor.authorChen, Jiangen
dc.contributor.authorLippold, Kumikoen
dc.contributor.authorMonavarfeshani, Aboozaren
dc.contributor.authorCarrillo, Gabriela Lizanaen
dc.contributor.authorJenkins, Rchaelen
dc.contributor.authorFox, Michael A.en
dc.description.abstractInhibitory synapses comprise only ∼20% of the total synapses in the mammalian brain but play essential roles in controlling neuronal activity. In fact, perturbing inhibitory synapses is associated with complex brain disorders, such as schizophrenia and epilepsy. Although many types of inhibitory synapses exist, these disorders have been strongly linked to defects in inhibitory synapses formed by Parvalbumin-expressing interneurons. Here, we discovered a novel role for an unconventional collagen—collagen XIX—in the formation of Parvalbumin+ inhibitory synapses. Loss of this collagen results not only in decreased inhibitory synapse number, but also in the acquisition of schizophrenia-related behaviors. Mechanistically, these studies reveal that a proteolytically released fragment of this collagen, termed a matricryptin, promotes the assembly of inhibitory nerve terminals through integrin receptors. Collectively, these studies not only identify roles for collagen-derived matricryptins in cortical circuit formation, but they also reveal a novel paracrine mechanism that regulates the assembly of these synapses.en
dc.description.sponsorshipBrain and Behavior Research Foundation NAR SAD Independent Investigator Awarden
dc.description.sponsorshipNational Institute of Healthen
dc.description.sponsorshipNIH: EY021222en
dc.description.sponsorshipVirginia Tech Carilion Research Institute Medical Researchen
dc.identifier.doi 10.1083/jcb.201509085en
dc.publisherRockefeller University Pressen
dc.rightsCreative Commons Attribution-NonCommercial-ShareAlike 3.0 Unporteden
dc.titleCollagen-derived matricryptins promote inhibitory nerve terminal formation in the developing neocortexen
dc.title.serialThe Journal of Cell Biologyen
dc.typeArticle - Refereeden
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