Bandorowicz-Pikula Joanna, Wos Marcin, Pikula Slawomir
Laboratory of Cellular Metabolism, Department of Biochemistry, Nencki Institute of Experimental Biology, PL 02-093 Warsaw, Poland.
Mol Membr Biol. 2012 Nov;29(7):229-42. doi: 10.3109/09687688.2012.693210. Epub 2012 Jun 14.
Annexins are physiologically important proteins that play a role in calcium buffering but also influence membrane structure, participate in Ca²⁺-dependent membrane repair events and in remodelling of the cytoskeleton. Thirty years ago several peptides isolated from lung perfusates, peritoneal leukocytes, neutrophiles and renal cells were proven inhibitory to the activity of phospholipase A₂. Those peptides were found to derive from structurally related proteins: annexins AnxA1 and AnxA2. These findings raised the question whether annexins may participate in regulation of the production of lipid second messengers and, therefore, modulate numerous lipid mediated signaling pathways in the cell. Recent advances in the field of annexins made also with the use of knock-out animal models revealed that these proteins are indeed important constituents of specific signaling pathways. In this review we provide evidence supporting the hypothesis that annexins, as membrane-binding proteins and organizers of the membrane lateral heterogeneity, may participate in lipid mediated signaling pathways by affecting the distribution and activity of lipid metabolizing enzymes (most of the reports point to phospholipase A₂) and of protein kinases regulating activity of these enzymes. Moreover, some experimental data suggest that annexins may directly interact with lipid metabolizing enzymes and, in a calcium-dependent or independent manner, with some of their substrates and products. On the basis of these observations, many investigators suggest that annexins are capable of linking Ca²⁺, redox and lipid signaling to coordinate vital cellular responses to the environmental stimuli.
膜联蛋白是具有重要生理功能的蛋白质，它们在钙缓冲过程中发挥作用，同时也会影响膜结构，参与钙离子依赖的膜修复过程以及细胞骨架的重塑。三十年前，从肺灌洗液、腹膜白细胞、中性粒细胞和肾细胞中分离出的几种肽被证明对磷脂酶A₂的活性具有抑制作用。这些肽被发现源自结构相关的蛋白质：膜联蛋白A1和膜联蛋白A2。这些发现引发了一个问题，即膜联蛋白是否可能参与脂质第二信使生成的调节，从而调节细胞内众多脂质介导的信号通路。膜联蛋白领域的最新进展，包括使用基因敲除动物模型所取得的成果，表明这些蛋白质确实是特定信号通路的重要组成部分。在这篇综述中，我们提供证据支持这样一个假说：膜联蛋白作为膜结合蛋白和膜侧向异质性的组织者，可能通过影响脂质代谢酶（大多数报道指向磷脂酶A₂）以及调节这些酶活性的蛋白激酶的分布和活性，参与脂质介导的信号通路。此外，一些实验数据表明，膜联蛋白可能直接与脂质代谢酶相互作用，并以钙依赖或非依赖的方式与它们的一些底物和产物相互作用。基于这些观察结果，许多研究人员认为膜联蛋白能够将钙离子、氧化还原和脂质信号联系起来，以协调细胞对环境刺激的重要反应。
