Department of Cellular and Molecular Medicine, Faculty of Medical and Health Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark.
Department of Biomedical Sciences, Faculty of Medical and Health Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark.
Mol Brain. 2017 Sep 4;10(1):43. doi: 10.1186/s13041-017-0324-9.
The neurotransmitter glutamate facilitates neuronal signalling at excitatory synapses. Glutamate is released from the presynaptic membrane into the synaptic cleft. Across the synaptic cleft glutamate binds to both ion channels and metabotropic glutamate receptors at the postsynapse, which expedite downstream signalling in the neuron. The postsynaptic density, a highly specialized matrix, which is attached to the postsynaptic membrane, controls this downstream signalling. The postsynaptic density also resets the synapse after each synaptic firing. It is composed of numerous proteins including a family of Discs large associated protein 1, 2, 3 and 4 (DLGAP1-4) that act as scaffold proteins in the postsynaptic density. They link the glutamate receptors in the postsynaptic membrane to other glutamate receptors, to signalling proteins and to components of the cytoskeleton. With the central localisation in the postsynapse, the DLGAP family seems to play a vital role in synaptic scaling by regulating the turnover of both ionotropic and metabotropic glutamate receptors in response to synaptic activity. DLGAP family has been directly linked to a variety of psychological and neurological disorders. In this review we focus on the direct and indirect role of DLGAP family on schizophrenia as well as other brain diseases.
神经递质谷氨酸在兴奋性突触处促进神经元信号传递。谷氨酸从前膜释放到突触间隙。在突触间隙中，谷氨酸与后膜上的离子通道和代谢型谷氨酸受体结合，加速神经元内的下游信号转导。突触后密度是一种高度特化的基质，附着在后膜上，控制着下游信号转导。突触后密度也在每次突触发射后重置突触。它由许多蛋白质组成，包括一个Discs large 相关蛋白 1、2、3 和 4（DLGAP1-4）家族，它们在后膜作为支架蛋白发挥作用。它们将谷氨酸受体与其他谷氨酸受体、信号蛋白和细胞骨架成分连接起来。由于在后膜的中央定位，DLGAP 家族似乎通过调节离子型和代谢型谷氨酸受体对突触活动的反应性，在突触可塑性中发挥着至关重要的作用。DLGAP 家族与各种心理和神经疾病直接相关。在这篇综述中，我们重点讨论了 DLGAP 家族在精神分裂症以及其他脑部疾病中的直接和间接作用。
