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Structural Basis of Teneurin-Latrophilin Interaction in Repulsive Guidance of Migrating Neurons.
Cell ( IF 45.5 ) Pub Date : 2020-01-09 , DOI: 10.1016/j.cell.2019.12.014 Daniel Del Toro 1 , Maria A Carrasquero-Ordaz 2 , Amy Chu 2 , Tobias Ruff 3 , Meriam Shahin 2 , Verity A Jackson 2 , Matthieu Chavent 4 , Miguel Berbeira-Santana 2 , Goenuel Seyit-Bremer 3 , Sara Brignani 3 , Rainer Kaufmann 5 , Edward Lowe 2 , Rüdiger Klein 3 , Elena Seiradake 2
Cell ( IF 45.5 ) Pub Date : 2020-01-09 , DOI: 10.1016/j.cell.2019.12.014 Daniel Del Toro 1 , Maria A Carrasquero-Ordaz 2 , Amy Chu 2 , Tobias Ruff 3 , Meriam Shahin 2 , Verity A Jackson 2 , Matthieu Chavent 4 , Miguel Berbeira-Santana 2 , Goenuel Seyit-Bremer 3 , Sara Brignani 3 , Rainer Kaufmann 5 , Edward Lowe 2 , Rüdiger Klein 3 , Elena Seiradake 2
Affiliation
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Teneurins are ancient metazoan cell adhesion receptors that control brain development and neuronal wiring in higher animals. The extracellular C terminus binds the adhesion GPCR Latrophilin, forming a trans-cellular complex with synaptogenic functions. However, Teneurins, Latrophilins, and FLRT proteins are also expressed during murine cortical cell migration at earlier developmental stages. Here, we present crystal structures of Teneurin-Latrophilin complexes that reveal how the lectin and olfactomedin domains of Latrophilin bind across a spiraling beta-barrel domain of Teneurin, the YD shell. We couple structure-based protein engineering to biophysical analysis, cell migration assays, and in utero electroporation experiments to probe the importance of the interaction in cortical neuron migration. We show that binding of Latrophilins to Teneurins and FLRTs directs the migration of neurons using a contact repulsion-dependent mechanism. The effect is observed with cell bodies and small neurites rather than their processes. The results exemplify how a structure-encoded synaptogenic protein complex is also used for repulsive cell guidance.
中文翻译：
Teneurin-Latrophilin相互作用在迁移神经元排斥引导中的结构基础。
Teneurins是古老的后生动物细胞粘附受体，可控制高等动物的大脑发育和神经元接线。细胞外C末端结合粘附GPCR Latrophilin，形成具有突触功能的跨细胞复合物。但是，Teneurins，Latrophilins和FLRT蛋白也在小鼠皮质细胞迁移的早期发育阶段表达。在这里，我们介绍了Teneurin-Latrophilin复合物的晶体结构，揭示了Latrophilin的凝集素和olfactomedin结构域如何跨过Teneurin（YD壳）的螺旋β桶结构域结合。我们将基于结构的蛋白质工程技术与生物物理分析，细胞迁移分析以及子宫内电穿孔实验相结合，以探讨相互作用在皮质神经元迁移中的重要性。我们表明结合亲铁蛋白和Teneurins的Latrophilins和FLRTs使用依赖于接触排斥的机制指导神经元的迁移。观察到的是细胞体和小的神经突而不是其过程的影响。结果例证了如何将结构编码的突触蛋白复合物也用于排斥细胞的指导。
更新日期：2020-01-10
中文翻译：
Teneurin-Latrophilin相互作用在迁移神经元排斥引导中的结构基础。
Teneurins是古老的后生动物细胞粘附受体，可控制高等动物的大脑发育和神经元接线。细胞外C末端结合粘附GPCR Latrophilin，形成具有突触功能的跨细胞复合物。但是，Teneurins，Latrophilins和FLRT蛋白也在小鼠皮质细胞迁移的早期发育阶段表达。在这里，我们介绍了Teneurin-Latrophilin复合物的晶体结构，揭示了Latrophilin的凝集素和olfactomedin结构域如何跨过Teneurin（YD壳）的螺旋β桶结构域结合。我们将基于结构的蛋白质工程技术与生物物理分析，细胞迁移分析以及子宫内电穿孔实验相结合，以探讨相互作用在皮质神经元迁移中的重要性。我们表明结合亲铁蛋白和Teneurins的Latrophilins和FLRTs使用依赖于接触排斥的机制指导神经元的迁移。观察到的是细胞体和小的神经突而不是其过程的影响。结果例证了如何将结构编码的突触蛋白复合物也用于排斥细胞的指导。
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