Shi Lei, Fu Amy Ky, Ip Nancy Y
Department of Biochemistry; Molecular Neuroscience Center; State Key Laboratory of Molecular Neuroscience; The Hong Kong University of Science and Technology; Clear Water Bay, Hong Kong, China.
Commun Integr Biol. 2010 Nov;3(6):622-4. doi: 10.4161/cib.3.6.13481. Epub 2010 Nov 1.
Synapse remodeling, which involves changes in the synaptic structure and their molecular composition, is required for the maturation and refinement of neural circuits. Although synapse remodeling is known to be tightly dependent on the assembly of local actin cytoskeleton, how actin directs the structural changes of synapse and targeting of synaptic proteins are not fully understood. Recently, we identified ephexin1, a Rho guanine nucleotide exchange factor (GEF) that regulates actin dynamics, to play an essential role in the maturation and functioning of the mammalian neuromuscular junction (NMJ). We showed that ephexin1 regulates the synaptic organization of the neurotransmitter receptor acetylcholine receptor (AChR) clusters through RhoA-dependent actin reorganization. Interestingly, ephexin1 has been implicated in the regulation of postsynaptic structure as well as the presynaptic vesicle release at various types of synapses. Our findings thus establish a novel function of ephexin1 in synapse remodeling through regulating the synaptic targeting of neurotransmitter receptors, revealing a versatile role of ephexin1 at synapses.
突触重塑涉及突触结构及其分子组成的变化，是神经回路成熟和精细化所必需的。虽然已知突触重塑紧密依赖于局部肌动蛋白细胞骨架的组装，但肌动蛋白如何指导突触的结构变化以及突触蛋白的靶向作用尚不完全清楚。最近，我们鉴定出ephexin1，一种调节肌动蛋白动力学的Rho鸟嘌呤核苷酸交换因子（GEF），它在哺乳动物神经肌肉接头（NMJ）的成熟和功能中起重要作用。我们发现ephexin1通过RhoA依赖的肌动蛋白重组来调节神经递质受体乙酰胆碱受体（AChR）簇的突触组织。有趣的是，ephexin1已被证明参与多种类型突触的突触后结构调节以及突触前囊泡释放。因此，我们的研究结果通过调节神经递质受体的突触靶向作用，确立了ephexin1在突触重塑中的新功能，揭示了ephexin1在突触中的多种作用。
