Prohibitin: A Novel Molecular Player in KDEL Receptor Signalling.
Prohibitin: A Novel Molecular Player in KDEL Receptor Signalling.
复制标题
DOI：
10.1155/2015/319454
复制
发表时间：
2015
影响因子：
--
通讯作者：
Sallese M
中科院分区：
文献类型：
--
作者：
Giannotta M;Fragassi G;Tamburro A;Vanessa C;Luini A;Sallese M
KDEL受体（KDELR）是一种七跨膜结构域蛋白，参与蛋白伴侣从高尔基复合体到内质网的逆行转运。我们最近的研究结果表明，高尔基体定位的KDELR作为一个功能性G蛋白偶联受体的结合和激活Gs和Gq。这些G蛋白诱导PKA和Src的激活，并调节逆行和顺行高尔基体运输。在这里，我们使用了一个集成的免疫共沉淀和质谱方法，以确定抑制素-1（PHB）作为KDELR相互作用。PHB是一种多功能蛋白，参与信号转导、细胞周期控制和线粒体蛋白的稳定。我们提供的证据表明，耗尽的聚羟基丁酸酯诱导强烈的膜运输活动在ER-高尔基体界面，所揭示的GM 130阳性高尔基体小管的形成，和招聘的p115，β-COP，和GBF 1的高尔基复合体。也有大量的SEC 31募集到内质网出口部位。此外，没有PHB降低了高尔基体定位的KDELR的水平，从而阻止了高尔基体-Src的KDELR依赖性激活，并抑制了VSVG的高尔基体至质膜转运。我们提出了一个模型，据此与以前的研究结果（例如，RAS-RAF信号传导途径），PHB可作为信号传导支架蛋白以辅助KDELR依赖性Src活化。
The KDEL receptor (KDELR) is a seven-transmembrane-domain protein involved in retrograde transport of protein chaperones from the Golgi complex to the endoplasmic reticulum. Our recent findings have shown that the Golgi-localised KDELR acts as a functional G-protein-coupled receptor by binding to and activating Gs and Gq. These G proteins induce activation of PKA and Src and regulate retrograde and anterograde Golgi trafficking. Here we used an integrated coimmunoprecipitation and mass spectrometry approach to identify prohibitin-1 (PHB) as a KDELR interactor. PHB is a multifunctional protein that is involved in signal transduction, cell-cycle control, and stabilisation of mitochondrial proteins. We provide evidence that depletion of PHB induces intense membrane-trafficking activity at the ER–Golgi interface, as revealed by formation of GM130-positive Golgi tubules, and recruitment of p115, β-COP, and GBF1 to the Golgi complex. There is also massive recruitment of SEC31 to endoplasmic-reticulum exit sites. Furthermore, absence of PHB decreases the levels of the Golgi-localised KDELR, thus preventing KDELR-dependent activation of Golgi-Src and inhibiting Golgi-to-plasma-membrane transport of VSVG. We propose a model whereby in analogy to previous findings (e.g., the RAS-RAF signalling pathway), PHB can act as a signalling scaffold protein to assist in KDELR-dependent Src activation.
登录
查看更多内容
影响因子：
--
作者：
Polier, Gemot;Neumann, Jennifer;Li-Weber, Min
通讯作者：
Li-Weber, Min
影响因子：
64.8
作者：
LEWIS, MJ;PELHAM, HRB
通讯作者：
PELHAM, HRB
DOI：
10.1016/j.bbamcr.2009.05.008
发表时间：
2009-08-01
影响因子：
5.1
作者：
Ande, Sudharsana R.;Gu, Yuanyuan;Mishra, Suresh
通讯作者：
Mishra, Suresh
影响因子：
4.3
作者：
Rajalingam, K;Rudel, T
通讯作者：
Rudel, T
影响因子：
21.3
作者：
Pulvirenti, Teodoro;Giannotta, Monica;Luini, Alberto
通讯作者：
Luini, Alberto