Collagen-derived matricryptins promote inhibitory nerve terminal formation in the developing neocortex.
Collagen-derived matricryptins promote inhibitory nerve terminal formation in the developing neocortex.
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DOI：
10.1083/jcb.201509085
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发表时间：
2016-03-14
期刊：
影响因子：
--
通讯作者：
Fox MA
中科院分区：
文献类型：
--
作者：
Su J;Chen J;Lippold K;Monavarfeshani A;Carrillo GL;Jenkins R;Fox MA
胶原蛋白XIX的蛋白水解释放片段，称为matricryptin，通过整联蛋白受体促进抑制性神经末梢的组装。抑制性突触仅占哺乳动物脑中突触总数的约20%，但在控制神经元活动中起重要作用。事实上，干扰抑制性突触与复杂的脑部疾病有关，例如精神分裂症和癫痫。尽管存在许多类型的抑制性突触，但这些病症与由表达小清蛋白的中间神经元形成的抑制性突触中的缺陷密切相关。在这里，我们发现了一种非传统的胶原蛋白-胶原蛋白XIX-在小清蛋白+抑制性突触的形成中的新作用。这种胶原蛋白的丢失不仅会导致抑制性突触数量减少，还会导致精神分裂症相关行为的获得。从机制上讲，这些研究表明，这种胶原蛋白的蛋白水解释放片段，称为matricryptin，通过整合素受体促进抑制性神经末梢的组装。总的来说，这些研究不仅确定了胶原衍生的matricryptins在皮质回路形成中的作用，而且还揭示了一种新的旁分泌机制，调节这些突触的组装。
A proteolytically released fragment of collagen XIX, termed a matricryptin, promotes the assembly of inhibitory nerve terminals through integrin receptors. 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.