活细胞中 Klothobeta (KLB) 和成纤维细胞生长因子受体 1 (FGFR1) 的动力学和分布揭示了成纤维细胞生长因子 21 (FGF21) 诱导的受体复合物。,Journal of Biological Chemistry

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活细胞中 Klothobeta (KLB) 和成纤维细胞生长因子受体 1 (FGFR1) 的动力学和分布揭示了成纤维细胞生长因子 21 (FGF21) 诱导的受体复合物。
Journal of Biological Chemistry ( IF 4.0 ) Pub Date : 2012 Jun 8 , DOI: 10.1074/jbc.m111.325670
Aaron Y K Ming ₁ , Eunjong Yoo , Eugene N Vorontsov , Svetlana M Altamentova , Dawn M Kilkenny , Jonathan V Rocheleau

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FGF21 在共表达 Klothobeta (KLB) 的细胞中刺激 FGFR1c 活性；然而，对这些受体在质膜上的相互作用知之甚少。我们使用光漂白和数量和亮度分析后的荧光恢复测量了活细胞中荧光蛋白标记的 KLB 和 FGFR1c 的动态和分布。我们证实荧光蛋白标记的 KLB 易位至质膜，并在与 FGFR1c 共表达时具有活性。FGF21 诱导的信号在用乳糖（半乳糖凝集素晶格的竞争性抑制剂）处理的细胞中得到增强，表明晶格结合调节 KLB 和/或 FGFR1c 活性。光漂白分析后的荧光恢复一致表明，乳糖处理增加了质膜上的 KLB 迁移率，但不影响 FGFR1c 的移动性。内源性 KLB 与半乳糖凝集素晶格的关联也通过与半乳糖凝集素 3 的免疫共沉淀得到证实。当与 FGFR1c 共表达时，KLB 迁移率增加，表明这两种受体形成独立于半乳糖凝集素晶格的异源复合物。数量和亮度分析表明，KLB 和 FGFR1c 分别在质膜上表现为单体和二聚体。共表达导致 KLB 和 FGFR1c 的单体表达，与 1:1 异源复合物的形成一致。随后添加 FGF21 诱导 FGFR1 二聚化而不改变 KLB 聚集体大小，表明形成了 1:2 KLB-FGFR1c 信号复合物。总的来说，这些数据表明 KLB 和 FGFR1 形成了一个 1:1 的异质复合物，独立于转变为 1 的半乳糖凝集素晶格：

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Dynamics and Distribution of Klothobeta (KLB) and fibroblast growth factor receptor-1 (FGFR1) in living cells reveal the fibroblast growth factor-21 (FGF21)-induced receptor complex.

FGF21 stimulates FGFR1c activity in cells that co-express Klothobeta (KLB); however, relatively little is known about the interaction of these receptors at the plasma membrane. We measured the dynamics and distribution of fluorescent protein-tagged KLB and FGFR1c in living cells using fluorescence recovery after photobleaching and number and brightness analysis. We confirmed that fluorescent protein-tagged KLB translocates to the plasma membrane and is active when co-expressed with FGFR1c. FGF21-induced signaling was enhanced in cells treated with lactose, a competitive inhibitor of the galectin lattice, suggesting that lattice-binding modulates KLB and/or FGFR1c activity. Fluorescence recovery after photobleaching analysis consistently revealed that lactose treatment increased KLB mobility at the plasma membrane, but did not affect the mobility of FGFR1c. The association of endogenous KLB with the galectin lattice was also confirmed by co-immunoprecipitation with galectin-3. KLB mobility increased when co-expressed with FGFR1c, suggesting that the two receptors form a heterocomplex independent of the galectin lattice. Number and brightness analysis revealed that KLB and FGFR1c behave as monomers and dimers at the plasma membrane, respectively. Co-expression resulted in monomeric expression of KLB and FGFR1c consistent with formation of a 1:1 heterocomplex. Subsequent addition of FGF21 induced FGFR1 dimerization without changing KLB aggregate size, suggesting formation of a 1:2 KLB-FGFR1c signaling complex. Overall, these data suggest that KLB and FGFR1 form a 1:1 heterocomplex independent of the galectin lattice that transitions to a 1:2 complex upon the addition of FGF21.

更新日期：2017-01-31

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