Institute of Anatomy II, Goethe-University Frankfurt, D-60590 Frankfurt am Main, Germany.
Neuropathology, Institute for Pathology, Carl Gustav Carus University Hospital, TU Dresden, D-01307 Dresden, Germany.
Int J Mol Sci. 2019 Aug 2;20(15):3776. doi: 10.3390/ijms20153776.
Astrocytes are increasingly perceived as active partners in physiological brain function and behaviour. The structural correlations of the glia-synaptic interaction are the peripheral astrocyte processes (PAPs), where ezrin and radixin, the two astrocytic members of the ezrin-radixin-moesin (ERM) family of proteins are preferentially localised. While the molecular mechanisms of ERM (in)activation appear universal, at least in mammalian cells, and have been studied in great detail, the actual ezrin and radixin kinases, phosphatases and binding partners appear cell type specific and may be multiplexed within a cell. In astrocytes, ezrin is involved in process motility, which can be stimulated by the neurotransmitter glutamate, through activation of the glial metabotropic glutamate receptors (mGluRs) 3 or 5. However, it has remained open how this mGluR stimulus is transduced to ezrin activation. Knowing upstream signals of ezrin activation, ezrin kinase(s), and membrane-bound binding partners of ezrin in astrocytes might open new approaches to the glial role in brain function. Ezrin has also been implicated in invasive behaviour of astrocytomas, and glial activation. Here, we review data pertaining to potential molecular interaction partners of ezrin in astrocytes, with a focus on PKC and GRK2, and in gliomas and other diseases, to stimulate further research on their potential roles in glia-synaptic physiology and pathology.
星形胶质细胞越来越被认为是生理脑功能和行为的积极参与者。胶质突触相互作用的结构相关性是周围星形胶质细胞突起（PAPs），其中 ezrin 和 radixin 是 ezrin-radixin-moesin（ERM）蛋白家族的两种星形胶质细胞成员，优先定位于此处。虽然 ERM（失活）激活的分子机制似乎在哺乳动物细胞中至少是普遍存在的，并且已经被详细研究过，但实际的 ezrin 和 radixin 激酶、磷酸酶和结合伴侣似乎具有细胞类型特异性，并且可能在一个细胞内被多路复用。在星形胶质细胞中，ezrin 参与过程运动，这可以通过神经递质谷氨酸刺激，通过激活神经胶质代谢型谷氨酸受体（mGluR）3 或 5 来实现。然而，这种 mGluR 刺激如何转导为 ezrin 激活仍然是开放的。了解 ezrin 激活的上游信号、ezrin 激酶和 ezrin 在星形胶质细胞中的膜结合结合伴侣，可能为星形胶质细胞在大脑功能中的作用开辟新的途径。ezrin 还与星形细胞瘤和神经胶质细胞的侵袭行为和激活有关。在这里，我们回顾了与星形胶质细胞中 ezrin 的潜在分子相互作用伙伴相关的数据，重点是 PKC 和 GRK2，以及在神经胶质瘤和其他疾病中，以刺激对它们在胶质突触生理学和病理学中的潜在作用的进一步研究。
