Leibniz Group "Dendritic Organelles and Synaptic Function," Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany; RG Neuroplasticity, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany.
Leibniz Group "Dendritic Organelles and Synaptic Function," Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany; RG Neuroplasticity, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany.
Cell Rep. 2023 Jul 25;42(7):112692. doi: 10.1016/j.celrep.2023.112692. Epub 2023 Jun 24.
The complex cytoarchitecture of neurons poses significant challenges for the maturation of synaptic membrane proteins. It is currently unclear whether locally secreted synaptic proteins bypass the Golgi or whether they traffic through Golgi satellites (GSs). Here, we create a transgenic GS reporter mouse line and show that GSs are widely distributed along dendrites and are capable of mature glycosylation, in particular sialylation. We find that polysialylation of locally secreted NCAM takes place at GSs. Accordingly, in mice lacking a component of trans-Golgi network-to-plasma membrane trafficking, we find fewer GSs and significantly reduced PSA-NCAM levels in distal dendrites of CA1 neurons that receive input from the temporoammonic pathway. Induction of long-term potentiation at those, but not more proximal, synapses is severely impaired. We conclude that GSs serve the need for local mature glycosylation of synaptic membrane proteins in distal dendrites and thereby contribute to rapid changes in synaptic strength.
神经元的复杂细胞结构对突触膜蛋白的成熟提出了重大挑战。目前尚不清楚局部分泌的突触蛋白是否绕过高尔基体,还是通过高尔基体卫星(GS)运输。在这里,我们创建了一个转基因 GS 报告小鼠品系,并表明 GS 广泛分布在树突上,并且能够进行成熟的糖基化,特别是唾液酸化。我们发现局部分泌的 NCAM 的多唾液酸化发生在 GS 上。因此,在缺乏跨高尔基网络到质膜运输成分的小鼠中,我们发现 CA1 神经元远端树突中的 GS 数量减少,并且 PSA-NCAM 水平显著降低,这些神经元接收来自颞侧弓状核通路的输入。在那些而不是更近端的突触诱导长时程增强会严重受损。我们得出结论,GS 满足了远端树突中突触膜蛋白局部成熟糖基化的需求,从而有助于突触强度的快速变化。