title: Collagen-derived matricryptins promote inhibitory nerve terminal formation in the developing neocortex.
abstract: Inhibitory 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.
authors.affiliation: Virginia Tech Carilion Research Institute, Roanoke, VA 24016.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Su
authors.affiliation: Virginia Tech Carilion Research Institute, Roanoke, VA 24016.
authors.forename: Jiang
authors.initials: J
authors.lastname: Chen
authors.affiliation: Virginia Tech Carilion Research Institute, Roanoke, VA 24016.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Lippold
authors.affiliation: Virginia Tech Carilion Research Institute, Roanoke, VA 24016 Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061.
authors.forename: Aboozar
authors.initials: A
authors.lastname: Monavarfeshani
authors.affiliation: Virginia Tech Carilion Research Institute, Roanoke, VA 24016.
authors.forename: Gabriela Lizana
authors.initials: GL
authors.lastname: Carrillo
authors.affiliation: Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061.
authors.forename: Rachel
authors.initials: R
authors.lastname: Jenkins
authors.affiliation: Virginia Tech Carilion Research Institute, Roanoke, VA 24016 Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 mafox1@vtc.vt.edu.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Fox
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism*; D007395:Interneurons / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019579:Neocortex / Q000378:metabolism* / Q000502:physiology*; D009411:Nerve Endings / Q000378:metabolism* / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology*; D010320:Parvalbumins / Q000378:metabolism; D012559:Schizophrenia / Q000378:metabolism / Q000503:physiopathology; D013569:Synapses / Q000378:metabolism / Q000502:physiology
chemical_list: D010320:Parvalbumins; D003094:Collagen