Secretion of VEGF-165 has unique characteristics, including shedding from the plasma membrane.
Secretion of VEGF-165 has unique characteristics, including shedding from the plasma membrane.
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DOI：
10.1091/mbc.e13-07-0418
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发表时间：
2014-04
影响因子：
3.3
通讯作者：
Balla T
中科院分区：
文献类型：
--
作者：
Guzmán-Hernández ML;Potter G;Egervári K;Kiss JZ;Balla T
使用VEGF 165-GFP嵌合体研究VEGF分泌。有效的分泌需要Sar 1和Arf 1依赖的步骤和高尔基体中的糖基化。VEGF保留在质膜的外表面，与其他膜成分一起脱落是分泌过程中的重要步骤。血管内皮生长因子（VEGF）是内皮细胞分化和血管生成的重要调节因子，在肿瘤的发生和血管形成过程中起着重要作用。VEGF-165是一种主要的形式，通过一种特征不明确的途径从细胞中分泌。在这里，我们使用绿色荧光蛋白和表位标记的VEGF-165，并发现其早期运输之间的内质网和高尔基体需要的小GTP结合蛋白Sar 1和Arf 1，其在高尔基体区室的糖基化是必要的有效后高尔基体运输和分泌的细胞。VEGF分泌的相对温度不敏感性及其Sar 1和Arf 1抑制谱将其与使用“组成性”分泌途径的其他货物区分开来。VEGF分泌的突出特征是蛋白质保留在质膜的外表面上，并且通过Ca 2+和蛋白激酶C刺激其分泌。重要的是，VEGF-165与其他膜组分一起从细胞表面脱落似乎是一个独特的特征，通过该特征，一些VEGF被递送到周围环境以发挥其已知的生物学作用。了解血管内皮生长因子运输可以揭示其他手段，肿瘤血管形成可以抑制药物干预。
VEGF secretion is studied using VEGF165-GFP chimera. Efficient secretion requires Sar1- and Arf1-dependent steps and glycosylation in the Golgi. VEGF is retained in the outer surface of the plasma membrane, and shedding with other membrane components is an important step in the secretion process. Vascular endothelial growth factor (VEGF) is a critical regulator of endothelial cell differentiation and vasculogenesis during both development and tumor vascularization. VEGF-165 is a major form that is secreted from the cells via a poorly characterized pathway. Here we use green fluorescent protein– and epitope-tagged VEGF-165 and find that its early trafficking between the endoplasmic reticulum and the Golgi requires the small GTP-binding proteins Sar1 and Arf1 and that its glycosylation in the Golgi compartment is necessary for efficient post-Golgi transport and secretion from the cells. The relative temperature insensitivity of VEGF secretion and its Sar1 and Arf1 inhibitory profiles distinguish it from other cargoes using the “constitutive” secretory pathway. Prominent features of VEGF secretion are the retention of the protein on the outer surface of the plasma membrane and the stimulation of its secretion by Ca2+ and protein kinase C. Of importance, shedding of VEGF-165 from the cell surface together with other membrane components appears to be a unique feature by which some VEGF is delivered to the surroundings to exert its known biological actions. Understanding VEGF trafficking can reveal additional means by which tumor vascularization can be inhibited by pharmacological interventions.