Neuropilin 1 binds PDGF-D and is a co-receptor in PDGF-D-PDGFRβ signaling
Neuropilin 1 binds PDGF-D and is a co-receptor in PDGF-D-PDGFRβ signaling
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DOI：
10.1242/jcs.200493
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发表时间：
2017-04-15
影响因子：
4
通讯作者：
Eriksson, Ulf
中科院分区：
文献类型：
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作者：
Muhl, Lars;Folestad, Erika Bergsten;Eriksson, Ulf
血小板源性生长因子 (PDGF)-D 是一种 PDGF 受体 β (PDGFR β) 特异性配体，与心血管疾病和癌症等多种病理状况有关，但其生物学功能仍不完全清楚。在这项研究中，我们证明 PDGF-D 以需要 PDGF-D C 端精氨酸残基的方式直接与神经毡蛋白 1 (NRP1) 结合。 PDGF-D（而非 PDGF-B）刺激可诱导成纤维细胞中 PDGFR beta-NRP1 复合物的形成。此外，PDGF-D 独立于 PDGFR β 诱导 NRP1 易位至内皮细胞中的细胞-细胞连接处，从而改变了 NRP1 对 VEGF-A-VEGFR2 信号传导的可用性。与 PDGF-B 相比，PDGF-D 在离体发芽测定中显示出对周细胞行为的不同影响。此外，PDGFD诱导的PDGFRβ-NRP1相互作用可以在位于不同细胞（内皮细胞和周细胞）的分子之间反式发生。总之，我们表明 NRP1 可以作为 PDGF-D-PDGFR β 信号传导的共同受体，并且可能与血管壁的细胞间通讯有关。
Platelet-derived growth factor (PDGF)-D is a PDGF receptor beta (PDGFR beta)-specific ligand implicated in a number of pathological conditions, such as cardiovascular disease and cancer, but its biological function remains incompletely understood. In this study, we demonstrate that PDGF-D binds directly to neuropilin 1 (NRP1), in a manner that requires the PDGF-D C-terminal Arg residue. Stimulation with PDGF-D, but not PDGF-B, induced PDGFR beta-NRP1 complex formation in fibroblasts. Additionally, PDGF-D induced translocation of NRP1 to cell-cell junctions in endothelial cells, independently of PDGFR beta, altering the availability of NRP1 for VEGF-A-VEGFR2 signaling. PDGF-D showed differential effects on pericyte behavior in ex vivo sprouting assays compared to PDGF-B. Furthermore, PDGFD- induced PDGFR beta-NRP1 interaction can occur in trans between molecules located in different cells (endothelial cells and pericytes). In summary, we show that NRP1 can act as a co-receptor for PDGF-D-PDGFR beta signaling and is possibly implicated in intercellular communication in the vascular wall.