Golf Samantha R, Trotter Justin H, Wang Jinzhao, Nakahara George, Han Xiao, Wernig Marius, Südhof Thomas C
Dept. of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
bioRxiv. 2025 Jan 6:2023.04.10.536254. doi: 10.1101/2023.04.10.536254.
Astrocytes perform multifarious roles in the formation, regulation, and function of synapses in the brain, but the mechanisms involved are incompletely understood. Interestingly, astrocytes abundantly express neuroligins, postsynaptic adhesion molecules that function as synaptic organizers by binding to presynaptic neurexins. Here we examined the function of neuroligins in astrocytes with a rigorous genetic approach that uses the conditional deletion of all major neuroligins () in astrocytes and complemented this approach by a genetic deletion of neuroligins in glia cells that are co-cultured with human neurons. Our results show that early postnatal deletion of neuroligins from astrocytes in vivo has no detectable effect on cortical or hippocampal synapses and does not alter the cytoarchitecture of astrocytes when evaluated in young adult mice. Moreover, deletion of astrocytic neuroligins in co-cultures of human neurons produced no detectable consequences for the formation and function of synapses. Thus, astrocytic neuroligins are unlikely to fundamentally shape synapse formation or astrocyte morphogenesis but likely perform other important roles that remain to be discovered.
星形胶质细胞在大脑突触的形成、调节和功能中发挥着多种作用,但其涉及的机制尚未完全明确。有趣的是,星形胶质细胞大量表达神经连接蛋白,这些突触后黏附分子通过与突触前神经配蛋白结合而作为突触组织者发挥作用。在此,我们采用严格的遗传学方法研究了星形胶质细胞中神经连接蛋白的功能,该方法利用条件性敲除星形胶质细胞中所有主要的神经连接蛋白(),并通过在与人类神经元共培养的神经胶质细胞中基因敲除神经连接蛋白来补充这一方法。我们的结果表明,在体内从星形胶质细胞中早期产后敲除神经连接蛋白对皮质或海马突触没有可检测到的影响,并且在年轻成年小鼠中评估时不会改变星形胶质细胞的细胞结构。此外,在人类神经元共培养物中敲除星形胶质细胞的神经连接蛋白对突触的形成和功能没有产生可检测到的影响。因此,星形胶质细胞的神经连接蛋白不太可能从根本上塑造突触形成或星形胶质细胞形态发生,但可能发挥其他有待发现的重要作用。