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-Structure paper
タイトル | Architecture and regulation of a GDNF-GFRα1 synaptic adhesion assembly. |
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ジャーナル・号・ページ | Nat Commun, Vol. 14, Issue 1, Page 7551, Year 2023 |
掲載日 | 2023年11月20日 |
著者 | F M Houghton / S E Adams / A S Ríos / L Masino / A G Purkiss / D C Briggs / F Ledda / N Q McDonald / |
PubMed 要旨 | Glial-cell line derived neurotrophic factor (GDNF) bound to its co-receptor GFRα1 stimulates the RET receptor tyrosine kinase, promoting neuronal survival and neuroprotection. The GDNF-GFRα1 ...Glial-cell line derived neurotrophic factor (GDNF) bound to its co-receptor GFRα1 stimulates the RET receptor tyrosine kinase, promoting neuronal survival and neuroprotection. The GDNF-GFRα1 complex also supports synaptic cell adhesion independently of RET. Here, we describe the structure of a decameric GDNF-GFRα1 assembly determined by crystallography and electron microscopy, revealing two GFRα1 pentamers bridged by five GDNF dimers. We reconsitituted the assembly between adhering liposomes and used cryo-electron tomography to visualize how the complex fulfils its membrane adhesion function. The GFRα1:GFRα1 pentameric interface was further validated both in vitro by native PAGE and in cellulo by cell-clustering and dendritic spine assays. Finally, we provide biochemical and cell-based evidence that RET and heparan sulfate cooperate to prevent assembly of the adhesion complex by competing for the adhesion interface. Our results provide a mechanistic framework to understand GDNF-driven cell adhesion, its relationship to trophic signalling, and the central role played by GFRα1. |
リンク | Nat Commun / PubMed:37985758 / PubMed Central |
手法 | EM (サブトモグラム平均) / EM (トモグラフィー) / X線回折 |
解像度 | 2.66 - 21.7 Å |
構造データ | EMDB-18400: GDNF/GFRa1 cell adhesion complex cryo-ET structure EMDB-18651: GDNF/GFRa1 cell adhesion complex bridging between adhering liposomes. PDB-8os6: |
化合物 | ChemComp-NAG: ChemComp-HOH: |
由来 |
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キーワード | CELL ADHESION / Adhesion / Synapse / Complex / signalling |