Structural insights into the in situ assembly of clustered protocadherin γB4.

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Tác giả: Fabao Chen, Zhen Fang, Tingting Feng, Luqiang Guo, Yongning He, Hongyu Hu, Yingbin Liu, Lihui Xin, Yang Yu, Ze Zhang, Zihan Zhang

Ngôn ngữ: eng

Ký hiệu phân loại: 133.594 Types or schools of astrology originating in or associated with a

Thông tin xuất bản: England : Nature communications , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 167169

Clustered protocadherins (cPcdhs) belong to the cadherin superfamily and play important roles in neural development. cPcdhs mediate homophilic adhesion and lead to self-avoidance and tiling by giving neurons specific identities in vertebrates. Structures and functions of cPcdhs have been studied extensively in past decades, but the mechanisms behind have not been fully understood. Here we investigate the in situ assembly of cPcdh-γB4, a member in the γ subfamily of cPcdhs, by electron tomography and find that the full length cPcdh-γB4 does not show regular organization at the adhesion interfaces. By contrast, cPcdh-γB4 lacking the intracellular domain can generate an ordered zigzag pattern between cells and the cis-interacting mode is different from the crystal packing of the ectodomain. We also identify the residues on the ectodomain that might be important for the zigzag pattern formation by mutagenesis. Furthermore, truncation mutants of the intracellular domain reveal different assembly patterns between cell membranes, suggesting that the intracellular domain plays a crucial role in the intermembrane organization of cPcdh-γB4. Taken together, these results suggest that both ectodomain and intracellular domain regulate the in situ assembly of cPcdh-γB4 for homophilic cell adhesion, thereby providing mechanistic insights into the functional roles of cPcdhs during neuronal wiring.
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