在体内有一个控制突触形成和维持的分子代码，目前还比较稀缺。在这里，我们发现分泌的蛋白质Adamtsl3通过跨膜受体DCC（结肠癌缺失基因）起着重要的海马突触组织器的作用。传统上，DCC的功能与谷氨酸能突触发生和对Netrin-1信号的可塑性相关联。我们证明，在神经元早期出生后删除Adamtsl3会影响DCC蛋白的表达，导致谷氨酸能突触和GABA能突触的密度降低。删除成年时期的Adamtsl3中的GABA能神经元或谷氨酸能神经元并不会干扰DCC-Netrin-1在谷氨酸能突触上的功能，但会控制DCC在GABA能突触上的信号传导。Adamtsl3-DCC信号传导单元还对GABA能突触的活动依赖性调适至关重要，包括DCC磷酸化和Src激酶激活。这些发现可能与精神分裂症特别相关，因为Adamtsl3和DCC的遗传变异已经独立地与患者的精神分裂症相关联。版权所有©2023作者。由Elsevier Inc.出版。保留所有权利。

The molecular code that controls synapse formation and maintenance in vivo has remained quite sparse. Here, we identify that the secreted protein Adamtsl3 functions as critical hippocampal synapse organizer acting through the transmembrane receptor DCC (deleted in colorectal cancer). Traditionally, DCC function has been associated with glutamatergic synaptogenesis and plasticity in response to Netrin-1 signaling. We demonstrate that early post-natal deletion of Adamtsl3 in neurons impairs DCC protein expression, causing reduced density of both glutamatergic and GABAergic synapses. Adult deletion of Adamtsl3 in either GABAergic or glutamatergic neurons does not interfere with DCC-Netrin-1 function at glutamatergic synapses but controls DCC signaling at GABAergic synapses. The Adamtsl3-DCC signaling unit is further essential for activity-dependent adaptations at GABAergic synapses, involving DCC phosphorylation and Src kinase activation. These findings might be particularly relevant for schizophrenia because genetic variants in Adamtsl3 and DCC have been independently linked with schizophrenia in patients.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.