Regulation of hippocampal excitatory synapse development by the adhesion G-protein coupled receptor brain-specific angiogenesis inhibitor 2 (BAI2/ADGRB2)

IF 2.4 3区医学 Q3 NEUROSCIENCES

Molecular and Cellular Neuroscience Pub Date : 2025-05-30 DOI:10.1016/j.mcn.2025.104015

Christina M. Meyer, Olga Vafaeva, Henry Low, David J. Speca, Elva Díaz

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引用次数: 0

Abstract

Glutamatergic synapses and their associated dendritic spines are critical information processing sites within the brain. Proper development of these specialized cellular junctions is important for normal brain functionality. Synaptic adhesion G protein-coupled receptors (aGPCRs) have been identified as regulators of synapse development and function. While two members of the Brain-specific angiogenesis inhibitor (BAI/ADGRB) subfamily of synaptic aGPCRs, BAI1/ADGRB1 and BAI3/ADGRB3, have been found to mediate synapse and spine formation, BAI2/ADGRB2 function remains uncharacterized at the synapse. Here, we show that endogenous ADGRB2 is expressed throughout the nervous system with prominent expression in synapse dense regions of the hippocampus. In dissociated hippocampal cultures, ADGRB2 is highly enriched at large postsynaptic sites, defined by the size of the postsynaptic scaffold PSD95. Loss of ADGRB2 negatively impacts glutamatergic synapses across development in dissociated hippocampal cultures. In contrast, GABAergic synapse density is unchanged. Furthermore, ADGRB2 deficient neurons have significant alterations in spine morphology with decreased density of mature PSD95-containing mushroom-shaped spines compared with wild-type neurons. Interestingly, no major alterations in dendritic complexity were observed in ADGRB2 deficient neurons, in contrast to previous results for the other BAIs/ADGRBs. The reduction in mature mushroom-shaped spines is commensurate with a reduction in spine volume and head diameter. Altogether, these results demonstrate that the aGPCR ADGRB2 is an important regulator of glutamatergic synapse and PSD95-associated spine development in cultured hippocampal neurons. These results expand the knowledge of the BAI/ADGRB subfamily of aGPCRs in mediating excitatory synapse and spine development and highlight differences unique to ADGRB2.

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粘附g蛋白偶联受体脑特异性血管生成抑制剂2 （BAI2/ADGRB2）对海马兴奋性突触发育的调控

谷氨酸突触及其相关的树突棘是大脑中重要的信息处理位点。这些特化细胞连接的适当发育对正常的脑功能很重要。突触粘附G蛋白偶联受体（agpcr）已被确定为突触发育和功能的调节因子。虽然脑特异性血管生成抑制剂（BAI/ADGRB）突触agpcr亚家族的两个成员BAI1/ADGRB1和BAI3/ADGRB3已被发现介导突触和脊柱形成，但BAI2/ADGRB2在突触中的功能仍未被表征。在这里，我们发现内源性ADGRB2在整个神经系统中表达，在海马突触密集区表达突出。在分离的海马培养物中，ADGRB2在大突触后位点高度富集，这是由突触后支架PSD95的大小决定的。在分离的海马培养中，ADGRB2的缺失会对谷氨酸突触的发育产生负面影响。相比之下，gaba能突触密度不变。此外，与野生型神经元相比，ADGRB2缺陷神经元的脊柱形态发生了显著改变，含psd95的成熟蘑菇状脊柱密度降低。有趣的是，与其他BAIs/ adgrb相比，ADGRB2缺陷神经元的树突复杂性没有发生重大变化。成熟蘑菇状脊柱的减少与脊柱体积和头部直径的减少是相称的。总之，这些结果表明，aGPCR ADGRB2是培养海马神经元中谷氨酸突触和psd95相关脊柱发育的重要调节因子。这些结果扩大了对介导兴奋性突触和脊柱发育的agpcr的BAI/ADGRB亚家族的认识，并突出了ADGRB2特有的差异。

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来源期刊

Molecular and Cellular Neuroscience 医学-神经科学

CiteScore

5.60

自引率

0.00%

发文量

审稿时长

37 days

期刊介绍： Molecular and Cellular Neuroscience publishes original research of high significance covering all aspects of neurosciences indicated by the broadest interpretation of the journal''s title. In particular, the journal focuses on synaptic maintenance, de- and re-organization, neuron-glia communication, and de-/regenerative neurobiology. In addition, studies using animal models of disease with translational prospects and experimental approaches with backward validation of disease signatures from human patients are welcome.