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首页> 外文期刊>Molecular and Cellular Biology >Different Routes of Bone Morphogenic Protein (BMP) Receptor Endocytosis Influence BMP Signaling
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Different Routes of Bone Morphogenic Protein (BMP) Receptor Endocytosis Influence BMP Signaling

机译：骨形态发生蛋白（BMP）受体胞吞作用的不同途径影响BMP信号传导。

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摘要

Endocytosis is important for a variety of functions in eukaryotic cells, including the regulation of signaling cascades via transmembrane receptors. The internalization of bone morphogenetic protein (BMP) receptor type I (BRI) and type II (BRII) and its relation to signaling were largely unexplored. Here, we demonstrate that both receptor types undergo constitutive endocytosis via clathrin-coated pits (CCPs) but that only BRII undergoes also caveola-like internalization. Using several complementary approaches, we could show that (i) BMP-2-mediated Smad1/5 phosphorylation occurs at the plasma membrane in nonraft regions, (ii) continuation of Smad signaling resulting in a transcriptional response requires endocytosis via the clathrin-mediated route, and (iii) BMP signaling leading to alkaline phosphatase induction initiates from receptors that fractionate into cholesterol-enriched, detergent-resistant membranes. Furthermore, we show that BRII interacts with Eps15R, a constitutive component of CCPs, and with caveolin-1, the marker protein of caveolae. Taken together, the localization of BMP receptors in distinct membrane domains is prerequisite to their taking different endocytosis routes with specific impacts on Smad-dependent and Smad-independent signaling cascades.
机译：内吞作用对于真核细胞的多种功能很重要，包括通过跨膜受体调节信号级联反应。 I型骨形态发生蛋白（BMP）受体和II型（BRII）受体的内在化及其与信号传导的关系尚待探索。在这里，我们证明两种受体类型都通过网格蛋白包被的凹坑（CCPs）经历组成型内吞作用，但只有BRII也会经历小窝样内在化。使用几种互补的方法，我们可以显示（i）BMP-2介导的Smad1 / 5磷酸化发生在非筏区域的质膜上，（ii）继续Smad信号传导导致转录反应需要通过网格蛋白介导的途径进行内吞（iii）导致碱性磷酸酶诱导的BMP信号传导是从受体开始的，这些受体分馏成富含胆固醇，耐去污剂的膜。此外，我们显示BRII与CCP的组成成分Eps15R相互作用，并与小窝蛋白的标记蛋白caveolin-1相互作用。总之，BMP受体在不同的膜结构域中的定位是它们采取不同的内吞途径的先决条件，这些途径对Smad依赖性和Smad依赖性信号传导级联具有特定影响。

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